Dental wear patterns reveal dietary ecology and season of death in a historical chimpanzee population

Dental wear analyses have been widely used to interpret the dietary ecology in primates. However, it remains unclear to what extent a combination of wear analyses acting at distinct temporal scales can be beneficial in interpreting the tooth use of primates with a high variation in their intraspecific dietary ecology. Here, we combine macroscopic tooth wear (occlusal fingerprint analysis, long-term signals) with microscopic 3D surface textures (short-term signals) exploring the tooth use of a historical western chimpanzee population from northeastern Liberia with no detailed dietary records. We compare our results to previously published tooth wear and feeding data of the extant and continually monitored chimpanzees of Taї National Park in Ivory Coast. Macroscopic tooth wear results from molar wear facets of the Liberian population indicate only slightly less wear when compared to the Taї population. This suggests similar long-term feeding behavior between both populations. In contrast, 3D surface texture results show that Liberian chimpanzees have many and small microscopic wear facet features that group them with those Taї chimpanzees that knowingly died during dry periods. This coincides with historical accounts, which indicate that local tribes poached and butchered the Liberian specimens during dust-rich dry periods. In addition, Liberian females and males differ somewhat in their 3D surface textures, with females having more microscopic peaks, smaller hill and dale areas and slightly rougher wear facet surfaces than males. This suggests a higher consumption of insects in Liberian females compared to males, based on similar 3D surface texture patterns previously reported for Taї chimpanzees. Our study opens new options for uncovering details of feeding behaviors of chimpanzees and other living and fossil primates, with macroscopic tooth wear tracing the long-term dietary and environmental history of a single population and microscopic tooth wear addressing short-term changes (e.g. seasonality)

Ligelizumab for Chronic Spontaneous Urticaria

Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332. opens in new tab.

Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one‐year extension study

Background Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks. Results Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown. Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged ( 2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders(Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation(FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2 –) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m s−1; P = 0.001). These changes persisted at days 12–14, and after allometricallyscaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio ( 19%, P 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2 – increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r=−0.53) and chronic (n = 7, r=−0.69; P 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n=11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspiredO2 fraction (FIO2 )=0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7±1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling

Wskaźniki odchowu i wartość dietetyczna mięsa kurcząt brojlerów w zależności od kompozycji zbóż w mieszankach natłuszczonych olejem sojowym i lnianym

The experiment was carried out on 200 ROSS 308 broiler chickens that were randomly assigned to 5 equal groups (K, D1, D2, D3, D4). The birds were fed the mixtures Starter (1–21 days of rearing) and Grower/Finisher (21–42 days) oiled with a mixture of soybean oil (3%) and linseed oil (3%). Two different grains represented the experimental factor, and were added to the mixtures in a 1:1 ratio, according to the following design: group K (control) – maize and wheat, group D1 – wheat and barley, group D2 – wheat and triticale, group D3 – maize and barley, group D4 – maize and triticale. It was shown that chickens fed the mixtures with triticale at age 42 days had significantly (P ≤ 0.01) higher body weight than those that received mixtures with barley. In the whole period of rearing, a significantly (P ≤ 0.05) lower feed conversion ratio was found in chickens fed diets containing wheat and barley, as compared with the control group. The used mixtures did not influence musculature and the proportion of skin with subcutaneous fat in carcasses; however, a significantly (P ≤ 0.05) lower abdominal fat level was found in carcasses of chicken fed mixtures containing wheat and triticale and wheat and barley, as comparer with the broilers from other groups (K, D3 and D4). No effect of feeding on the content of most fatty acids in the lipids of leg muscles was found, while the breast muscles of the birds receiving the mixture with wheat and barley have shown a significant decrease in the proportion of linolenic acid and an increase in stearic acid. There were no significant effects of grain composition in mixtures in terms of muscle pH or sensory properties of the meat; they had, however, an impact on its color.Doświadczenie przeprowadzono na 200 kurczętach brojlerach ROSS 308, które rozdzielono losowo do 5. równolicznych grup (K, Dl, D2, D3, D4). Kurczęta żywiono mieszankami Starter (1-21 dni) i Grower/Finiszer (22-42 dni) natłuszczonymi mieszaniną oleju sojowego (3%) i lnianego (3%). Czynnikiem różnicującym grupy były 2 zboża wprowadzone do mieszanek w udziale 1:1 wg układu: grupa K (kontrolna) - kukurydza i pszenica; grupa D1 - pszenica i jęczmień, grupa D2 - pszenica i pszenżyto, grupa D3 - kukurydza i jęczmień, grupa D4 - kukurydza i pszenżyto. Wykazano, że kurczęta żywione mieszankami z pszenżytem w wieku 42 dni uzyskały istotnie (P ≤ 0,01) wyższe masy ciała niż otrzymujące mieszanki z jęczmieniem. Istotnie (P ≤ 0,05) niższym zużyciem paszy w całym okresie odchowu w odniesieniu do grupy kontrolnej charakteryzowały się kurczęta żywione dietami zawierającymi pszenicę i pszenżyto. Stosowane mieszanki nie wpłynęły na umięśnienie i udział skóry z tłuszczem podskórnym w tuszkach, natomiast wykazano istotnie (P ≤ 0,05) mniej tłuszczu sadełkowego w tuszkach kurcząt żywionych mieszankami z udziałem pszenicy i pszenżyta oraz pszenicy i jęczmienia w porównaniu do ptaków z pozostałych grup (K, D3 i D4). Nie stwierdzono wpływu żywienia na udział większości kwasów tłuszczowych w lipidach mięśni nóg, natomiast w mięśniach piersiowych ptaków otrzymujących mieszanki z pszenicą i jęczmieniem wykazano istotne obniżenie ilości kwasu linolenowego oraz zwiększenie stearynowego. Nie odnotowano istotnego oddziaływania kompozycji zbóż w mieszankach na odczyn mięśni, jak też na wyróżniki smakowe, natomiast miały one wpływ na jego barwę

Wall temperature measurements within a high-power inductive plasma discharge

Electromagnetic plasma generators (inductive and helicon) are commonly used for planetary entry simulation and increasingly for electric propulsion applications. However, one obstacle in increasing the power and efficiency of these systems is a lack of knowledge regarding the distribution of tube wall temperature. The tube wall temperature acts as a mechanical limit to the thruster/generator operating conditions and is directly related to the distribution of thermal energy within the discharge volume. This paper presents the results of an experimental investigation to determine spatially resolved wall temperatures in a 180 kW inductive plasma generator. This investigation showed that significant wall heating does not occur until the midpoint of the inductive coil, increasing rapidly to reach peak temperature over a distance 15&amp;#x0025; of the total tube. During this rapid heating phase, one-third of the total tube heat flux is produced, assisting in quantifying previously observed mechanical failures due to thermal stress. The peak temperature difference between inner and outer wall surfaces was recorded as 619.1 K, approximately twice that of the previously proposed limit which considered integral rather than spatially resolved values. Using the results of this investigation, a refined estimate of critical wall temperatures for various tube thicknesses has been developed, allowing more targeted cooling systems to be implemented in the future generator designs.</p