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Provision of high-quality care and ensuring retention of children on antiretroviral therapy (ART) are essential to reduce human immunodeficiency virus (HIV)-associated morbidity and mortality. Virological non-suppression (≥1000 viral copies/ml) is an indication of suboptimal HIV care and support. This retrospective cohort study included ART-naïve children who initiated first-line ART between July 2015 and August 2017 in Johannesburg and rural Mopani district. Of 2739 children started on ART, 29.5% (807/2739) were lost to care at the point of analysis in August 2018. Among retained children, overall virological non-suppression was 30.2% (469/1554). Virological non-suppression was associated with higher loss to care 30.3% (229/755) compared with suppressed children (9.7%, 136/1399, P < 0.001). Receiving treatment in Mopani was associated with virological non-suppression in children under 5 years (adjusted odds ratio (aOR) 1.7 (95% confidence interval (CI) 1.1–2.4), 5–9 years (aOR 1.8 (1.1–3.0)) and 10–14 years (aOR 1.9 (1.2–2.8)). Virological non-suppression was associated with lower CD4 count in children 5–9 years (aOR 2.1 (1.1–4.1)) and 10–14 years (aOR 2.1 (1.2–3.8)). Additional factors included a shorter time on ART (<5 years aOR 1.8–3.7 (1.3–8.2)), and male gender (5–9 years, aOR1.5 (1.01–2.3)), and receiving cotrimoxazole prophylaxis (10–14 years aOR 2.0 (1.2–3.6)). In conclusion, virological non-suppression is a factor of subsequent programme loss in both regions, and factors affecting the quality of care need to be addressed to achieve the third UNAIDS 90 in paediatric HIV.
Although anorectal Chlamydia trachomatis (CT) infections are frequently diagnosed in men who have sex with men (MSM) and women, the reason for this infection often remains unexplained, as anal sex is not always reported. Oropharyngeal infections inoculating the gastrointestinal (GI) tract may contribute to anorectal-CT infections, as evidence in animals suggests that chlamydia bacteria undergo GI passage; however, no evidence exists in humans. Longitudinal patient clinic-registry data from MSM (n = 17 125) and women (n = 4120) from two Dutch sexually transmitted infection clinics were analysed. When adjusting for confounding socio-demographics, co-infections and risk behaviour, previous (from 3 weeks up to 24 months) oropharyngeal CT was not a risk factor for subsequent anorectal CT in women (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.18–1.18; P = 0.11) and MSM (OR 1.33; 95% CI 0.86–2.07; P = 0.204). Despite the large dataset, the numbers did not allow for the estimation of risk in specific subgroups of interest. The role of the GI tract cannot be excluded with this epidemiological study, but the impact of preceding oropharyngeal CT on anorectal-CT infection is likely limited.
Relational victimization typically emerges first during the elementary school period, and has been associated with increased levels of internalizing symptoms in children. Individual differences in autonomic nervous system functioning have been suggested as a potential factor linking social stressors and internalizing symptoms. The aim of this study was therefore to examine whether heart rate and heart rate variability mediated the association between relational victimization and internalizing symptoms in 373 mainstream elementary school children. Children were assessed in 2015 (T0; Grades 3–5, M age = 9.78 years, 51% boys) and reassessed in 2016 (T1). Heart rate and heart rate variability were assessed during a regular school day at T1. A multi-informant (teacher and peer report) cross-time measure of relational victimization, and a multi-informant (self- and teacher report) measure of internalizing problems at T1 was used. Results showed that heart rate variability, but not heart rate, mediated the association between relational victimization and internalizing symptoms. This study provides tentative support that in children from a general population sample, a psychobiological factor may mediate the association of relational victimization with internalizing symptoms.
In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; P<0.01; day 11: calm 1.83; nervous 1.57; P<0.05). Ovulation rate on day 11 in nervous ewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; P<0.01). Reproductive loss between days 30 and 74 represented 7.3% of the overall loss. Temperament did not affect concentrations of progesterone, but nervous ewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect differences in energy utilisation.
Development of collateral vessels, arteriogenesis, may protect against tissue ischemia, however, quantitative data on this process remain scarce. We have developed a technique for replicating the entire arterial network of ischemic rat hindlimbs in three dimensions (3D) based on vascular casting and automated sequential cryo-imaging. Various dilutions of Batson’s No. 17 with methyl methacrylate were evaluated in healthy rats, with further protocol optimization in ischemic rats. Penetration of the resin into the vascular network greatly depended on dilution; the total length of casted vessels below 75 µm was 13-fold higher at 50% dilution compared with the 10% dilution. Dilutions of 25–30%, with transient clamping of the healthy iliac artery, were optimal for imaging the arterial network in unilateral ischemia. This protocol completely filled the lumina of small arterioles and collateral vessels. These appeared as thin anastomoses in healthy legs and increasingly larger vessels during ligation (median diameter 1 week: 63 µm, 4 weeks: 127 µm). The presented combination of quality casts with high-resolution cryo-imaging enables automated, detailed 3D analysis of collateral adaptation, which furthermore can be combined with co-registered 3D distributions of fluorescent molecular imaging markers reflecting biological activity or perfusion.
Cognitive impulsivity may increase children's risk of developing delinquent behavior. However, the influence of cognitive impulsivity may depend on social environmental risk factors. This study examined the moderating effect of late childhood parenting behaviors and peer relations on the influence of children's cognitive impulsivity on delinquency development across adolescence and early adulthood, while taking possible interactions with intelligence also into account. Delinquent behavior of 412 boys from the Pittsburgh Youth Study was measured annually from ages 13 to 29 years with official arrest records. Cognitive impulsivity (neurocognitive test scores) and intelligence were assessed at age 12–13. Parenting behaviors (persistence of discipline, positive reinforcement, and parental knowledge), peer delinquency, and peer conventional activities were assessed between ages 10 and 13 years. Results showed that, while controlling for intelligence, the influence of youths' cognitive impulsivity on delinquency depended on their parents' behaviors. An interaction was found among cognitive impulsivity, intelligence, and peer delinquency, but instead of cognitive impulsivity, the effect of intelligence on delinquency was particularly moderated. Overall, findings suggest that when there was moderation, high cognitive impulsivity and low intelligence were associated with an increased probability for engaging in delinquency predominantly among boys in a good social environment, but not in a poor social environment.
Temperament can be defined as the fearfulness and reactivity of an animal in response to humans and strange, novel or threatening environments. The productive performance of an animal is affected by its temperament, and selection of calm animals might improve their adaptation to the farming environment and handling, as well as improve productivity. The temperament was measured in lambs of two breeds of sheep in Uruguay. The effects of dam’s age, type of birth, age of the lamb and contemporary group (CG; lambs belonging to the same year, flock, sex and rearing group) on the temperament of the lambs and the heritability of temperament were estimated with a Bayesian analysis using Gibbs sampling. Overall, 4962 Corriedale lambs and 2952 Merino lambs from 13 farms were tested. Temperament was measured using the isolation box test, isolating a lamb inside the box for 30 s, and recording the vibrations produced by its movements. The average temperament score (±s.e.m.) of the Corriedale lambs was 24.7 (±0.23) and that of the Merino was 36.8 (±0.45). Temperament was not associated with dam’s age, type of birth or lamb’s age. There were no relevant differences in the agitation score between lambs born in 2010 and 2011. The mean of the distribution of possible values of heritability (±s.d.) was 0.18 (±0.05) for the Corriedale and 0.31 (±0.06) for the Merino. The likelihood of heritability values to be greater than 0.15 exceeded 70% in the Corriedale and 90% in the Merino. The temperament of Merino and Corriedale sheep in Uruguay is moderately heritable. It is not related to dam’s age, type of birth or age of the lambs; however, it is affected by some aspect of the CG.
There is strong evidence that the gonads modulate the hypothalamic–pituitary–adrenal axis. To investigate these sex differences at the adrenal glands of sheep we compared the cortisol response to ACTH (experiment 1) and measured the relative expression of oestrogen receptor alpha (ERS1), androgen receptor (AR), melanocortin 2 receptor (MC2R) and steroid acute regulatory protein (STAR) mRNA in adrenal glands (experiment 2) of gonadectomised rams and ewes either with or without sex steroid replacement. In experiment 1 six castrated adult rams and four ovariectomised adult ewes were used in two ACTH trials. On each trial blood samples were taken every 15 min for 4 h through an indwelling jugular catheter and each animal received 0.5 mg of an ACTH analogue i.v., immediately after the sample at 1 h from the beginning of the trial. Four days after the first trial the males received 100 mg of Testosterone Cyclopentilpropionate (TC) i.m. and the females received 2.5 mg of Oestradiol Benzoate (EB) i.m. At 72 h after TC or EB administration the second trial was performed. In experiment 2 the adrenal glands were obtained from gonadectomised adult rams (n=8) and adult ewes (n=8). Four rams received 100 mg of TC i.m. and four females received 0.5 mg of EB i.m. Blood samples were taken at 0, 12, 24, 48 and 72 h relative to steroid replacement and the animals were thereafter slaughtered. Cortisol, testosterone and 17β-oestradiol were determined by radioimmunoanalysis. The transcripts of ERS1, AR, MC2R and STAR were determined by real-time reverse transcription PCR in adrenal tissue. Cortisol secretion was higher in female sheep than in male sheep, and higher in EB-treated than non-treated ewes. No difference in cortisol secretion was observed between TC-treated and non-treated rams. Gonadectomised rams treated with TC presented greater AR mRNA and MC2R mRNA expression than males without the steroid replacement. Gonadectomised ewes treated with EB tended to present lower AR mRNA than the ones without steroid replacement. Gonadectomised rams with TC also had greater AR mRNA, ERS1 mRNA and MC2R mRNA expression than ewes treated with EB. The relative amount of STAR transcript was not different among the different groups. The results confirm sex differences in ACTH-induced cortisol secretion in sheep, as well as in the expression of the receptor proteins for both 17β-oestradiol and testosterone in the sheep adrenal gland. However, the underlying mechanisms for sex steroid modulation remain unresolved.
Christian communities throughout the Middle Ages used the Bible as a tool for the education and edification of both the clergy and the laity. No other book in the Middle Ages invited commentary as the Bible did, and the sheer bulk of the material that has been preserved is impressive. Commentaries alone do not do justice to the wide range of scholarly writing that the Bible inspired. Lexicons, chronologies, concordances, versifications, and abridgments all attest to the primacy of the Bible as the medieval study book. Not all of this material is available today in print; much of it exists in manuscript only. Most of it is also forgotten or ignored by modern biblical interpreters, which is unfortunate. In modern Jewish circles, it is not uncommon to consult Rashi, a medieval interpreter, on matters of scriptural interpretation; by contrast, no equivalent for Rashi exists in the Christian tradition. The inaccessibility of the texts is partly to blame for this; of the medieval commentaries that are available in print, relatively few have been translated into modern languages. Another reason is that, as we have seen in the previous chapters, modern hermeneutical assumptions have shifted away from the questions that medieval commentaries asked of the text. Their reasoning seems hard to follow and often appears repetitive and unoriginal. The influence of patristic commentary on the medieval tradition is immense, to the extent that some scholars have dismissed the medieval exegetical tradition as purely derivative. As we will see later, however, this assessment does not do justice to the medieval commentary tradition. Although not everyone may agree that these medieval commentaries are relevant for modern theologians and preachers, read in their proper context, they can nevertheless give fascinating insights into a variety of aspects of medieval life, not just theology and biblical interpretation. The tradition of biblical interpretation touches on topics as diverse as science, education, psychology, and politics.
For a long time, even in the scholarly world, the history of the Bible in the Middle Ages was thought to be a field that held little interest except for a small group of specialists. This began to change shortly after World War II, with three important, almost simultaneous publications: in 1946, Ceslas Spicq published his Esquisse d'une histoire de l'exégèse latine au Moyen Âge (Sketch of a History of Latin Exegesis in the Middle Ages), a concise survey of medieval biblical exegesis. Spicq's Esquisse was almost exclusively based on a survey of the texts he found in Jean-Paul Migne's Patrologia Latina, a comprehensive printed edition of Latin patristic and medieval church writers from Tertullian (second century c.e.) to Innocent III (1215). For the period after the latter, Spicq limited himself to the few authors whose work was edited, while providing a handlist of authors whose work was available in manuscript only. In 1952, Beryl Smalley published her Study of the Bible in the Middle Ages, an epoch-making work, which showed that serious textual biblical studies began not with the Enlightenment but much earlier, in the Carolingian period, and reached an intellectual peak in the twelfth century. In contrast to Spicq, Smalley's work ventured into the vast array of unprinted texts in medieval collections, uncovering sometimes surprising aspects of medieval biblical scholarship and putting half-forgotten authors, such as Andrew of Saint Victor, back into the limelight. Like Spicq, however, Smalley left the work of the fourteenth- and fifteenth-century exegetes largely unexplored. Between 1959 and 1964, Henri de Lubac published his magisterial four-volume Exégèse médiévale. Les quatre sens de l’écriture (Medieval Exegesis. The Four Senses of Scripture), in which he demonstrated that the rich spiritual tradition of medieval exegesis had relevance for twentieth-century theology. In fact, Lubac argued, modern theology might have omitted an essential Christian element by discarding the patristic and medieval traditions of interpretation and one-sidedly embracing the Enlightenment historical-critical method. Since then, medieval exegesis has been a subject of serious scholarly attention and reappreciation.
The influence of the Bible in the Middle Ages was enormous. Whether read in private devotions, prayed in communal liturgy, commented on in classroom lectures, expounded on in sermons, painted on church walls, or sculpted in cathedral portals, its influence shaped not only moral and spiritual life but also intellectual, aesthetic, and social life. One cannot understand the medieval world without appreciating the scope of medieval people's engagement with biblical stories, characters, and images. Students of medieval history and religion are the primary intended audience for this book. It aims to provide them with a basic understanding of the medieval Bible, the formation and transmission of its text, and its traditions of interpretation. Although there are many introductions and handbooks to the Bible, most of these follow the historico-critical method, a tradition of biblical interpretation that has its origin in the Enlightenment. This method builds on the assumption that in order to retrieve the meaning of a text, we need first to establish its “original” form, study this within its historical context, and analyze what the author tried to convey to his intended audience. Thus, textbook introductions to the Bible tend to pay ample attention to biblical archaeology and to the historical context of the authors, editors, and redactors of the Hebrew and Greek texts. They typically offer linguistic analysis of the text and perhaps an historical survey of its transmission, including the formation of the canon. But they usually stop there. If they do include a history of biblical scholarship and interpretation, this usually starts with the Renaissance and Reformation. The Middle Ages are thus obscured from view, although the rich body of medieval biblical illustrations is often freely exploited for its aesthetic value.