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The role of natural selection in shaping biological diversity is an area of intense interest in modern biology. To date, studies of positive selection have primarily relied on genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects of population history. In particular, admixture between diverged populations can distort or hide prior selection events in modern genomes, though this process is not explicitly accounted for in most selection studies despite its apparent ubiquity in humans and other species. Through analyses of ancient and modern human genomes, we show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes. Our results imply that this canonical mode of selection has probably been underappreciated in the evolutionary history of humans and suggest that our current understanding of the tempo and mode of selection in natural populations may be inaccurate.

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic 'super-archaic' species-Homo luzonensis and H. floresiensis-were present around the time anatomically modern humans arrived in the region >50,000 years ago. Intriguingly, contemporary human populations across ISEA carry distinct genomic traces of ancient interbreeding events with Denisovans-a separate hominin lineage that currently lacks a fossil record in ISEA. To query this apparent disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes, including >200 from ISEA. Our results corroborate widespread Denisovan ancestry in ISEA populations, but fail to detect any substantial super-archaic admixture signals compatible with the endemic fossil record of ISEA. We discuss the implications of our findings for the understanding of hominin history in ISEA, including future research directions that might help to unlock more details about the prehistory of the enigmatic Denisovans.

© 2018 IFIP. The use of HTTPS as the only means to connect to web servers is increasing. It is being pushed from both sides: from the bottom up by client distributions and plugins, and from the top down by organisations such as Google. However, there are potential technical hurdles that might lock some clients out of the modern web. This paper seeks to measure and precisely quantify those hurdles in the wild. More than three million measurements provide statistically significant evidence of degradation. We show this through statistical techniques, in particular Rasch analysis, which also shows that various factors influence the problem ranging from the client's browser, to their locale.

Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49–45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.

Objective To investigate the mitigating effects of administration of local or systemic meloxicam on the electroencephalographic (EEG) and cardiovascular responses during surgical castration of Bos indicus bull calves. Study design Prospective, randomized, experimental study. Animals Thirty-six 6–8 month-old Bos indicus bull calves, with a mean ± standard deviation weight of 237 ± 19 kg. Methods Animals were randomly allocated to three groups of 12 (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes prior to castration; group M, 0.5 mg kg−1 of meloxicam subcutaneously 30 minutes prior to castration; group C, no pre-operative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9–1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle incision, T1). HR and MAP were compared at 10 second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the EEG (Ptot) were analysed using area under the curve comparing T1 to B. Results All EEG variables were significantly different between B and T1 (p ≤ 0.0001). No differences in F50 were found between groups during T1 (p = 0.6491). F95 and Ptot were significantly different between group L and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20–50 second periods. Conclusions The EEG changes indicate nociceptive responses in all three groups during surgical castration, greater in group L compared to groups C and M. Both analgesics attenuated the peracute cardiovascular response. Lidocaine and meloxicam administered prior to castration attenuated these responses in Bos indicus bull calves. Clinical relevance These findings provide support for the pre-operative administrat

The aim of this prospective, controlled, randomised trial was to develop a technique for mechanical nociceptive threshold testing (NTT) to assess pain in Bos indicus bull calves undergoing surgical castration. Analgesia was provided by 0.5 mg/kg subcutaneous (SC) meloxicam (M) and/or 2 mg/kg of intra-testicular and SC (at the surgery sites) lidocaine (L). Forty-eight Brahman bull calves at 6–8 months of age were divided into six study groups, each with eight animals: no surgery control; surgical castration (C) without analgesia; C and Mpre-op; C and Mpost-op; C, L and Mpost-op; C and L. Mechanical NTT was performed the day before surgery (Day –1) and on Days 1, 2, 6, 10 and 13 after surgery. A handheld manual pneumatic device with a 1-mm (diameter) blunt pin was used to deliver a mechanical stimulus to a maximum of 27 Newtons either side of the most dorsal aspect of the sacrum. The most frequent responses to the mechanical stimulus were lifting or kicking of the leg on the same side as the stimulus (31%) and stepping away from the stimulus (24.9%). Data were analysed with a mixed effect linear model with the nociceptive threshold (NT) as the response variable and day and analgesic treatment as predictors (P < 0.05 was considered significant). For all groups, there was a trend towards decreasing NT over the study period but there were no significant differences between groups. Step down model selection with day, batch and treatment terms revealed a significant effect of day (P < 0.001) and batch (P = 0.007). Mechanical NTT for assessment of pain in Bos indicus bull calves requires further refinement to determine if this is a useful method of pain assessment.

The aim was to compare rectal, pharyngeal and oesophageal temperature measurements in anaesthetized pigs. Data were compared using the Bland-Altman method, and correlation coefficients and error measures were calculated. Sixty-six sets of data were collected from 16 pigs weighing 16.2 +/- 4.2 kg. The bias (and 95% limit of agreement) for rectal and pharyngeal compared with oesophageal temperature were 0.69 (-1.18 to 2.57) degrees C and 0.22 (-0.84 to 1.28) degrees C, respectively. The correlation coefficients for rectal and pharyngeal compared with oesophageal temperature were 0.47 and 0.87, respectively. The absolute error for rectal and pharyngeal compared with oesophageal temperature was 0.7 +/- 0.9 degrees C and 0.2 +/- 0.5 degrees C, respectively. Pharyngeal temperature measurement may be more suitable than rectal temperature measurement for estimation of oesophageal temperature during general anaesthesia of pigs.

Objective: Analgesic regimes were compared in pregnant ewes after laparotomy by measuring thermal (TT) and mechanical (MT) nociceptive thresholds. Study design: Prospective randomised experimental study. Animals: Pregnant ewes at 121 days gestation underwent laparotomy as part of another research project. Methods: Thermal and mechanical thresholds were measured before, and 2, 6, 24 and 48 hours after surgery. Thermal stimuli were delivered to the lateral aspect of the metatarsus via a skin-mounted probe, and mechanical stimuli to the contralateral site via a pneumatically driven 1.5 mm diameter pin. Each test was performed five times, alternating thermal and mechanical stimuli, with ten minutes between thermal stimuli. At the end of surgery ewes received either: 75 μg hour-1 transdermal fentanyl patch (medial thigh) (group FP) (n = 8), or 3 μg kg-1hour-1 intra-peritoneal medetomidine via an osmotic pump (group IPM) (n = 8) inserted immediately prior to closure. Data were analysed using the Kruskal-Wallis RS Test (p < 0.05). Once a significant effect was identified, pairwise comparisons were performed using paired Wilcoxon RS tests. To compensate for multiple hypotheses testing, p < 0.005 was considered significant. Results: Prior to surgery mean ± SD TT was 56.1 ± 5.0 °C (FP) and 55.6 ± 5.0 °C (IPM); MT was 5.3 ± 2.6 N (FP) and 8.0 ± 5.0 N (IPM). In FP there was no significant change in either TT or MT over time. In IPM there was no significant change in MT over time but TT increased at two hours to 59.2 ± 3.0 °C (p = 0.003). Skin temperature (ST) ranged from 33.0 to 34.7 °C and did not change over time. There were no significant differences between groups in TT, MT or ST. Conclusions and clinical relevance: Administration of intra-peritoneal medetomidine (3 μg kg-1hour-1) by an osmotic pump increases the thermal nociceptive threshold in the immediate post operative period in pregnant sheep, suggesting that this agent may have a role in providing post-operative anal

To determine the accuracy of Doppler blood pressure measurement in anaesthetised pigs eight large white pigs (Sus scrofa) were anaesthetised with zolazepam and tiletamine as Zoletil 100 (4 mg/kg) and xylazine (2 mg/kg) by intramuscular injection followed by isoflurane in 100% oxygen. Blood pressure measurements were recorded using a Doppler probe on the radial artery and a catheter in the femoral artery connected to a transducer. The sample mean of the Doppler measurements were compared with the sample mean of the invasive systolic arterial blood pressure while accounting for the heart rate, end-tidal CO2 and temperature. The predicted error of the Doppler was greatest when pigs were hypotensive and normothermic: 11 mmHg (CI: 6-15). Doppler measurements should be interpreted with caution in anaesthetised pigs that are hypotensive and normothermic.