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The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD.
Methods:
Participants aged 18–50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively.
Results:
Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score.
Conclusion:
Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex
The taxonomy of the 10 recognized Neoechinorhynchus species associated with emydid turtles is complex due to the morphological conservatism. In the present study, specimens of N. emyditoides from northern and southeastern Mexico exhibit great phenotypic plasticity on its diagnostic characteristics. We sequenced three molecular markers: the internal transcribed spacers ITS1, ITS2 and 5.8S gene, the D2 + D3 domains of the large subunit from nuclear DNA and cytochrome c oxidase subunit I (cox1) from mitochondrial DNA. Sequences of the nuclear molecular markers were aligned and compared with other congeneric species associated with emydids available in GenBank. Phylogenetic analyses supported the polyphyly of Neoechinorhynchus. The species from emydids formed a clade, which was subdivided into five subclades that correspond with each species analysed (N. pseudemydis, N. chrysemydis, N. emydis, N. schmidti and N. emyditoides). To understand better the genetic structure of N. emyditoides a haplotype network was inferred with 29 cox1 sequences, revealing the presence of 13 haplotypes, two of which were shared and 11 were unique. The high values of fixation index, Fst (0.4227–0.8925) detected between the two populations from southeastern and the two from northern Mexico indicated low genetic flow among the populations. Our data suggest that the Neoechinorhynchus species associated with emydid turtles diversified in the eastern USA and that of N. emyditoides expanded its distribution range reached southeastern Mexico.
The objective of this study was verify the best waist-to-height ratio (WHtR) cutoff points for the prediction of insulin resistance (IR) according to stage of sexual maturation in Brazilian adolescents. Data were analyzed from 37,759 adolescents between 12-17 years of age, of both sexes, participating in the ERICA study on cardiovascular risk factors in adolescents (“Estudo de Riscos Cardiovasculares em Adolescentes – ERICA”). The following variables were included: sex, age, sexual maturity according to the Tanner stage, waist circumference, height, waist-to-height ratio, fasting insulin and fasting blood sugar so as to obtain the HOMA-IR. We constructed a ROC curve for each group in order to determine the best WHtR cutoff points for the sample stratified by sex and stratified by sex and sexual maturation stage. The female sex corresponded to 60% of the sample, with a mean age of 14.7 years (SD ±0.08 years) and 13.1 % had IR. The prediction of IR through the WHtR indicator was better for boys, where all the areas under the ROC curve were superior to 0.70. When stratifying by sex alone, the best WHtR cutoff points found were equal to 0.45 for girls and 0.44 for boys. When stratifying by Tanner maturation stages, the cut-off points were reduced with advancing sexual maturation in the male group, while the opposite occurred in the female group. Among Brazilian adolescents, WHtR is a good predictor of IR evaluated by HOMA-IR, but different cut-off points should be adopted according to sex and sexual maturation stage.
Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
The control of human visceral leishmaniasis (VL) is hard since there are no vaccines available as well as the treatment is hampered by toxicity and resistant parasites. Furthermore, as human, and canine VL causes immunosuppression, the combination of drugs with immunostimulatory agents is interesting to upregulate the immunity, reducing side-effects, improving treatment approaches against disease. Herein, we assessed the immunochemotherapy using miltefosine along with a vaccine formulated by Leishmania braziliensis antigens + saponin + monophosphoryl lipid-A (LBSapMPL) in L. infantum-infected hamsters. Two months after infection, the animals received treatments, and after 15 days they were evaluated for the treatment effect. The potential anti-Leishmania effect of miltefosine + LBSapMPL-vaccine was revealed by a specific immune response activation reflecting in control of spleen parasitism using half the miltefosine treatment time. The treated animals also showed an increase of total and T-CD4 splenocytes producing IFN-γ and TNF-α and a decrease of interleukin-10 and anti-Leishmania circulating IgG. In addition, it was demonstrated that the control of spleen parasitism is related to the generation of a protective Th1 immune response. Hence, due to the combinatorial action of miltefosine with LBSapMPL-vaccine in immunostimulating and controlling parasitism, this immunochemotherapy protocol can be an important alternative option against canine and human VL.
Four excavations have been performed at the archaeological site of Cova Rosa (Asturias, Cantabrian Spain): three of them in the second half of last century and the other in this decade. Although little of the archaeological material found in those excavations has been published, here we attempt the stratigraphic correlation of sections revealed by the different excavations and we present 22 new radiocarbon dates for bones and marine shells, built in a Bayesian statistical model. This has enabled the documentation of occupations that mainly took place during the Last Glacial period, in the Solutrean (middle and upper phases) and Magdalenian (archaic, lower, and upper phases), and also in the early Holocene (Mesolithic). These occupations are compared with the record at other sites in Cantabrian Spain in general and in Asturias, in particular.
The aim of this study was to assess body shape trajectories in childhood and midlife in relation to subsequent risk of breast cancer (BC) in a Mediterranean cohort.
Design:
The ‘Seguimiento Universidad de Navarra’ (SUN) Project is a dynamic prospective cohort study of university graduates initiated in 1999. With a group-based modelling approach, we assessed body shape trajectories from age 5 to 40 years. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for BC after the age of 40 years according to the body shape trajectory.
Setting:
City of Pamplona, in the North of Spain.
Participants:
6498 women with a mean age of 40 years (sd 9).
Results:
We identified four distinct body shape trajectories (‘childhood lean-midlife increase’ (19·9 %), ‘childhood medium-midlife stable’ (53 %), ‘childhood heavy-midlife stable’ (21 %) and ‘childhood heavy-midlife increase’ (6·1 %)). Among 54 978 women-years of follow-up, we confirmed eighty-two incident cases of BC. Women in the ‘childhood lean-midlife increase’ group showed a higher risk of BC (HR = 1·84, 95 % CI 1·11, 3·04) compared with women in the ‘childhood medium-midlife stable’ category. This association was stronger for postmenopausal BC (HR = 2·42, 95 % CI 1·07, 5·48).
Conclusions:
Our results suggest a role for lifetime adiposity in breast carcinogenesis.
To determine the optimal anthropometric cut-off points for predicting the likelihood ratios of hypertension and diabetes in the Peruvian population.
Design:
A cross-sectional study was performed to establish cut-off values for body mass index (BMI), waist circumference (WC), waist:height ratio (WHtR) and Conicity index (C-index) associated with increased risk of hypertension and diabetes. Youden’s index (YIndex), area under the curve (AUC), sensitivity and specificity were calculated.
Setting:
Peruvian households.
Participants:
Peruvian population over the age of 18 years.
Results:
A total of 31 553 subjects were included, 57 % being women. Among the women, 53·06 % belonged to the 25- to 44-year-old age group [mean age: 41·66 in men and 40·02 in women]. The mean BMI, WHtR and C-index values were higher in women 27·49, 0·61, 1·30, respectively, while the mean WC value was higher in men 92·12 cm (sd ± 11·28). The best predictors of hypertension in men were the WHtR (AUC = 0·64) and the C-index (AUC = 0·64) with an optimal cut-off point of 0·57 (YIndex = 0·284) and 1·301 (YIndex = 0·284), respectively. Women showed an AUC of 0·63 and 0·61 in the WHtR and C-index, respectively, with an optimal cut-off of 0·61 (YIndex = 0·236) and 1·323 (YIndex = 0·225). The best predictor for diabetes was the C-index: with an AUC = 0·67 and an optimal cut-off of 1·337 (YIndex = 0·346) for men and an AUC = 0·66 and optimal cut-off of 1·313 (YIndex = 0·319) for women.
Conclusions:
Our findings show that in Peruvian adults, the WHtR and the C-index have the strongest association with hypertension in both sexes. Likewise, the C-index had the strongest association with diabetes.
We conducted a quasi-experimental study to evaluate a bundle to prevent nonventilator hospital-acquired pneumonia (NV-HAP) in patients on enteral tube feeding. After the intervention, there was an increase in bundle compliance from 55.9% to 70.5% (P < .01) and a significant decrease (34%) in overall NV-HAP rates from 5.71 to 3.77 of 1,000 admissions.
The work described in this Research Communication concerns the production of Dulce de leche (DL), that is a traditional product from South America obtained by concentration. Maillard reaction (MR) products are mainly responsible for the formation of color and flavor in this product. Lactose-hydrolyzed products have been developed to supply consumer demand, but this hydrolysis may affect the flavor, color, taste, texture and even some nutritional aspects of the product. We studied the influence of different levels of lactose-hydrolysis, sucrose addition and initial pH on the development of MR, appraised by the determination of 5-hydroxymethylfurfural (HMF). A process simulator with multi-monitoring system was used to produce 15 DL. Box-Behnken 33 experimental design was applied for the three factors: pH, lactose-hydrolysis level and sucrose concentration. Lipids, protein, ashes, carbohydrates, water activity, dissolved solids, colorimetric analysis and HMF (free and total) are among the physicochemical attributes and MR indicators analyzed in this work. The products showed significant differences in composition but all the values were in agreement with the literature. Moreover, higher levels of lactose hydrolysis and higher pH presented a direct relation with the development of MR, observed by an increase in coloration (lower luminosity) and more formation of HMF, both free and total. The present study expands the knowledge about DL spread made of lactose-hydrolyzed milk, allowing the food industries to produce a lactose free DL with nutritional and sensory characteristics closer to the traditional product.
Our group has reported the imprint formation of biological material on polycarbonate nuclear track detectors by UV-C exposure, which is used as an approach to simultaneously visualize cell imprints and nuclear tracks coming from the boron neutron capture reaction. Considering that the cell nucleus has a higher UV-C absorption than the cytoplasm and that hematoxylin preferentially stains the nucleus, we proposed to enhance the contrast between these two main cell structures by hematoxylin staining before UV-C sensitization. In this study, several experiments were performed in order to optimize UV-C exposure parameters and chemical etching conditions for cell imprint formation using the SK-BR-3 breast cancer cell line. The proposed method improves significantly the resolution of the cell imprints. It allows clear differentiation of the nucleus from the rest of the cell, together with nuclear tracks pits. Moreover, it reduces considerably the UV-C exposure time, an important experimental issue. The proposed methodology can be applied to study the boron distribution independently from the chosen cell line and/or boron compounds.
Stereo-electroencephalography (SEEG) has been shown to be a valuable tool for the anatomo-electroclinic definition of the epileptogenic zone (EZ) in some patients with medically refractory epilepsy considered for surgery. In Spain, many of those patients are not offered this diagnostic procedure. The objective of our health technology assessment (HTA) report was to evaluate the effectiveness, safety and cost-effectiveness of SEEG to define the EZ in patients with refractory epilepsy considered for surgery compared to no SEEG intervention (i.e. remaining with further antiepileptic drugs).
Methods:
We undertook a systematic review with meta-analyses on the effectiveness and safety of SEEG. A cost-effectiveness analysis was conducted using a Markov model which simulates the costs and health outcomes of individuals for a lifetime horizon from the perspective of the Spanish National Health Service (NHS). The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.
Results:
The EZ was found in 92 percent of patients who underwent SEEG, 72 percent were eligible for epilepsy surgery and 33 percent were free of seizures after surgery (47 percent of those who received surgery). Any complications related to insertion and monitoring of SEEG and the subsequent intervention occurred in 1.3 percent of patients. In the base case analysis, SEEG led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio of EUR 10,368 (USD 12,217) per QALY. The sensitivity analyses showed that the results of the study were robust.
Conclusions:
SEEG is a cost-effective technology in patients with refractory epilepsy considered for surgery when compared to no SEEG intervention.
The family ${\mathcal{F}}_{\unicode[STIX]{x1D706}}$ of orientation-preserving harmonic functions $f=h+\overline{g}$ in the unit disc $\mathbb{D}$ (normalised in the standard way) satisfying
for some $\unicode[STIX]{x1D706}\in \unicode[STIX]{x2202}\mathbb{D}$, along with their rotations, play an important role among those functions that are harmonic and orientation-preserving and map the unit disc onto a convex domain. The main theorem in this paper generalises results in recent literature by showing that convex combinations of functions in ${\mathcal{F}}_{\unicode[STIX]{x1D706}}$ are convex.
Renewed excavations at FLK Zinj and its surrounding landscape have yielded valuable information regarding its paleoecological situation and the prehistoric behavioral function of the site. The density of materials at the main cluster of the site excavated by Leakey contrasts with the bone and lithic scatters surrounding the site. The location of FLK Zinj, situated a few hundred meters away from a freshwater spring, would have enabled hominins access to water, plants and game. The appeal of the spot for hominins (also explained by the presence of a wooded habitat) is confirmed by inferences of its redundant use prior and during the formation of the FLK Zinj paleosol, as witnessed by materials accumulated both under and on the waxy clay deposit that constitutes the FLK Zinj stratum. The single-cluster nature of the site indicates central-place behavior and evidence is provided that hominins occupied the site at a time of very low predation hazards in the area.
The records of early hominins are commonly localized both temporally and spatially even in archaeologically rich basins like Olduvai Gorge, Tanzania. The FLK North site was discovered in 1960, but the reason for the exact location of this dense concentration of fossils and stone tools on a lake-margin flat has not been explained. We present new geological and geochemical information from six excavations in upper Bed I, which revealed up to 1.4-m-thick carbonate deposits, attesting to the presence of freshwater springs in the area surrounding FLK North. The δ18O signatures of the tufa are typical for meteoric water that has evolved during evaporation. Tuff IF that caps the sequence was deposited on uneven topography with the highest area a low-relief ridge between two faults at the archaeological site and lowest areas being sites of groundwater discharge. The model proposed here is that rainfall on adjacent highlands was transported to the basin where faults acted as conduits for water. Similar hydrogeological settings at modern lakes Manyara and Eyasi, currently support lush groundwater forest and woodland despite arid climate. FLK North may have been an “oasis” offering freshwater and shelter for consuming meat by both carnivores and hominins.
Recent work at FLK North (FLK N) has unearthed a new archaeological assemblage recovered with precise control of its stratigraphic position. In the present work, the technological study of the new lithic sample is described. The results show the co-occurrence in the same site of different technological behaviors. At FLK N, hominins were involved in both percussion/battering activities and through freehand and bipolar knapping, in core reduction. However, the reconstruction of the operational sequences shows that core reduction was probably a marginal behavior, while percussion/battering activities occurred more regularly throughout the sequence. If hominins were not involved in regular carcass processing, as recent taphonomic studies suggest, then hominins' sporadic and low-impact visits to the site over a long period of time must have been driven by other activities probably linked to the exploitation of alternative resources. Plant processing could have been a plausible explanation for hominin presence at FLK N.
From excavation at FLK North levels 1–2 in 1960–1962, Mary Leakey reported approximately 1200 Oldowan artifacts and 3300 large mammal fossils as a hominin “living floor”. Preliminary taphonomic analysis by Bunn seemed supportive, based on the presence of some cut-marked bones, the concentration of several dozen bovid individuals, and the relative abundance of limbs and mandibles over other axial elements. Recent taphonomic analysis of Leakey's entire fossil assemblage by Domínguez-Rodrigo and Barba, however, documents a minor hominin role at the site, contrasted to the dominant role of carnivores. Felids brought prey animals; hyenas scavenged from abandoned felid meals. At different times, hominins butchered several bovids and discarded artifacts at this dynamic location. Since 2006, renewed excavations at FLK North and other sites by the Olduvai Paleoanthropology and Paleoecology Project (TOPPP) have expanded artifact and fossil samples and implemented new analytical approaches to clarify taphonomic histories of the Olduvai paleolandscape. At FLK North, > 1000 new large mammal fossils from levels 1 to 2 show minimal butchery evidence amid abundant evidence of carnivore gnawing/fracture, rodent gnawing, and sediment abrasion. To help guide future excavation and analyses, we have developed several alternative working hypotheses of site formation.
The 1959 discovery of the hominin fossil Zinjanthropus boisei brought the world's attention to the rich records at Olduvai Gorge, Tanzania. Subsequent excavations of archaeological level 22 (FLK Zinj) Bed I uncovered remains of Homo habilis and a high-density collection of fossils and Oldowan stone tools. The occurrence of this unusual collection of bones and tools at this specific location has been controversial for decades. We present paleoecological data that provide new insights into the origin of FLK Zinj. Our recent excavations 200 m north of the site uncovered a 0.5-m-thick tufa mound draped by Tuff IC, in the same stratigraphic horizon as level 22. Stable isotope analyses indicate that the carbonates were deposited by a freshwater spring. Phytolith analysis of the waxy clay under Tuff IC revealed abundant woody dicotyledon and palm phytoliths, indicating that the site was wooded to densely wooded. The time equivalency and close physical proximity of the two environments indicate the two are related. This study has provided the first documented evidence of springs in Bed I and these data have important implications for the interpretation of hominin behavior in meat acquisition and the ongoing debate on scavenging versus hunting.
FLK North is one of the densest concentrations of fossils found in Olduvai Gorge. A recent taphonomic re-evaluation of the collection excavated by Leakey at the site suggests that it was a palimpsest in which most of the animals were accumulated and modified by carnivores. The lithic tools therefore seem to have an independent depositional history from most of the fauna. The present study, based on new excavations, expands the evidence supporting this interpretation and demonstrates a thicker deposit than was reported by Leakey, including new archaeological levels. It also shows that in the few instances where hominins butchered carcasses, meat, not marrow, was their main target. This argues against passive scavenging hypotheses, which emphasize the dietary role of marrow, and instead underscores the importance of meat in the diet of early Pleistocene hominins.
The biological and genetic diversity of Neospora caninum is very limited because of availability of only a few viable isolates worldwide. This study describes the isolation and biological and molecular characterization of a new viable isolate of N. caninum (NC-SP1), from a cattle in Brazil. Approximately 400 g of brain from a naturally infected adult male cattle from an abattoir was fed to a 2-month-old dog. Neospora-like oocysts were observed on day 7 post-inoculation (PI) and the duration of oocyst shedding was 14 days. The DNA obtained from oocysts was characterized molecularly and the final sequence was 99% identical to homologous sequences of N. caninum available in GenBank®. For bioassay, gerbils (Meriones unguiculatus) were orally inoculated with 10 100 and 1000 oocysts; all gerbils remained clinically normal but developed N. caninum antibodies 14 days PI. Cell culture isolation was successful using the brain homogenate from one of the gerbils and tachyzoites were observed 24 days PI. Microsatellite genotyping revealed a unique genetic profile for this new reference isolate.