Now is the hour: Maori farewell song

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Recommended Joint and Meta‐Analysis Strategies for Case‐Control Association Testing of Single Low‐Count Variants

In genome‐wide association studies of binary traits, investigators typically use logistic regression to test common variants for disease association within studies, and combine association results across studies using meta‐analysis. For common variants, logistic regression tests are well calibrated, and meta‐analysis of study‐specific association results is only slightly less powerful than joint analysis of the combined individual‐level data. In recent sequencing and dense chip based association studies, investigators increasingly test low‐frequency variants for disease association. In this paper, we seek to (1) identify the association test with maximal power among tests with well controlled type I error rate and (2) compare the relative power of joint and meta‐analysis tests. We use analytic calculation and simulation to compare the empirical type I error rate and power of four logistic regression based tests: Wald, score, likelihood ratio, and Firth bias‐corrected. We demonstrate for low‐count variants (roughly minor allele count [MAC] < 400) that: (1) for joint analysis, the Firth test has the best combination of type I error and power; (2) for meta‐analysis of balanced studies (equal numbers of cases and controls), the score test is best, but is less powerful than Firth test based joint analysis; and (3) for meta‐analysis of sufficiently unbalanced studies, all four tests can be anti‐conservative, particularly the score test. We also establish MAC as the key parameter determining test calibration for joint and meta‐analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99692/1/gepi21742.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99692/2/gepi21742-sup-0010-figureS1.pd

Tilt and Translation Motion Perception during Off Vertical Axis Rotation

The effect of stimulus frequency on tilt and translation motion perception was studied during constant velocity off-vertical axis rotation (OVAR), and compared to the effect of stimulus frequency on eye movements. Fourteen healthy subjects were rotated in darkness about their longitudinal axis 10deg and 20deg off-vertical at 0.125 Hz, and 20deg offvertical at 0.5 Hz. Oculomotor responses were recorded using videography, and perceived motion was evaluated using verbal reports and a joystick with four degrees of freedom (pitch and roll tilt, mediallateral and anteriorposterior translation). During the lower frequency OVAR, subjects reported the perception of progressing along the edge of a cone. During higher frequency OVAR, subjects reported the perception of progressing along the edge of an upright cylinder. The modulation of both tilt recorded from the joystick and ocular torsion significantly increased as the tilt angle increased from 10deg to 20deg at 0.125 Hz, and then decreased at 0.5 Hz. Both tilt perception and torsion slightly lagged head orientation at 0.125 Hz. The phase lag of torsion increased at 0.5 Hz, while the phase of tilt perception did not change as a function of frequency. The amplitude of both translation perception recorded from the joystick and horizontal eye movements was negligible at 0.125 Hz and increased as a function of stimulus frequency. While the phase lead of horizontal eye movements decreased at 0.5 Hz, the phase of translation perception did not vary with stimulus frequency and was similar to the phase of tilt perception during all conditions. During dynamic linear acceleration in the absence of other sensory input (canal, vision) a change in stimulus frequency alone elicits similar changes in the amplitude of both self motion perception and eye movements. However, in contrast to the eye movements, the phase of both perceived tilt and translation motion is not altered by stimulus frequency. We conclude that the neural processing to distinguish tilt and translation linear acceleration stimuli differs between eye movements and motion perception

Adaptive strategies of African horse sickness virus to facilitate vector transmission

African horse sickness virus (AHSV) is an orbivirus that is usually transmitted between its equid hosts by adult Culicoides midges. In this article, we review the ways in which AHSV may have adapted to this mode of transmission. The AHSV particle can be modified by the pH or proteolytic enzymes of its immediate environment, altering its ability to infect different cell types. The degree of pathogenesis in the host and vector may also represent adaptations maximising the likelihood of successful vectorial transmission. However, speculation upon several adaptations for vectorial transmission is based upon research on related viruses such as bluetongue virus (BTV), and further direct studies of AHSV are required in order to improve our understanding of this important virus

Total knee arthroplasty in patients with severe obesity:outcomes of standard keeled tibial components versus stemmed universal base plates

Background: Patients with severe obesity [body mass index (BMI) ≥ 40 kg/m2] potentially overload the tibial component after total knee arthroplasty (TKA), risking tibial subsidence. Using a cemented single-radius cruciate-retaining TKA design, this study compared the outcomes of two tibial baseplate geometries in patients with BMI ≥ 40 kg/m2: standard keeled (SK) or universal base plate (UBP), which incorporates a stem. Methods: This was a retrospective, single-centre cohort study with minimum 2 years follow-up of 111 TKA patients with BMI ≥ 40 kg/m2: mean age 62.2 ± 8.0 (44–87) years, mean BMI 44.3 ± 4.6 (40–65.7) kg/m2 and 82 (73.9%) females. Perioperative complications, reoperations, alignment and patient-reported outcomes (PROMS): EQ-5D, Oxford Knee Score (OKS), Visual Analogue Scale (VAS) pain score and satisfaction were collected preoperatively, and at 1 year and final follow-up postoperatively. Results: Mean follow-up was 4.9 years. SK tibial baseplates were performed in 57 and UBP in 54. There were no significant differences in baseline patient characteristics, post-operative alignment, post-operative PROMs, reoperations or revisions between the groups. Three early failures requiring revision occurred: two septic failures in the UBP group and one early tibial loosening in the SK group. Five-year Kaplan–Meier survival for the endpoint mechanical tibial failure was SK 98.1 [94.4–100 95% confidence interval (CI)] and UBP 100% (p = 0.391). Overall varus alignment of the limb (p = 0.005) or the tibial component (p = 0.031) was significantly associated with revision and return to theatre. Conclusions: At early to mid-term follow-up, no significant differences in outcomes were found between standard and UBP tibial components in patients with BMI ≥ 40 kg/m2. Varus alignment of either tibial component or the limb was associated with revision and return to theatre.</p

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa

Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans

The effect of COVID-19 restrictions on rehabilitation and functional outcome following total hip and knee arthroplasty during the first wave of the pandemic

Aims: The primary aim was to assess the patient-perceived effect of restrictions imposed due to COVID-19 on rehabilitation following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Secondary aims were to assess perceived restrictions, influence on mental health, and functional outcome compared to patients undergoing surgery without restriction. Methods: During February and March 2020, 105 patients underwent THA (n = 48) or TKA (n = 57) and completed preoperative and six-month postoperative assessments. A cohort of 415 patients undergoing surgery in 2019 were used as the control. Patient demographic data, BMI, comorbidities, Oxford Hip Score (OHS) or Knee Score (OKS), and EuroQoL five-domain (EQ-5D) score were collected preoperatively and at six months postoperatively. At six months postoperatively, the 2020 patients were also asked to complete a questionnaire relating to the effect of the social restrictions on their outcome and their mental health. Results: Nearly half of the patients (47.6%, n = 50/105) felt that the restrictions imposed by COVID-19 had limited their rehabilitation and were associated with a significantly worse postoperative OKS (p < 0.001), EQ-5D score (p < 0.001), and lower satisfaction rate (p = 0.019). The reasons for the perceived limited rehabilitation were: being unable to exercise (n = 32, 64%), limited access to physiotherapy (n = 30, 60%), and no face-to-face follow-up (n = 30, 60%). A quarter (n = 26) felt that their mental health had deteriorated postoperatively; 17.1% (n = 18) felt depressed and 26.7% (n = 28) felt anxious. Joint-specific scores and satisfaction for the 2020 group were no different to the 2019 group, however patients undergoing THA in 2020 had a significantly worse postoperative EQ-5D compared to the 2019 cohort (difference 0.106; p = 0.001) which was not observed in patients undergoing TKA. Conclusion: Half of the 2020 cohort felt that their rehabilitation had been limited and was associated with worse postoperative Oxford and EQ-5D scores, and lower rates of patient satisfaction, but relative to the 2019 cohort their overall outcomes were no different, with the exception of THA patients who had a worse general health score. Level of evidence: Prospective study, Level 2

Spatial Coding of Eye Movements Relative to Perceived Orientations During Roll Tilt with Different Gravitoinertial Loads

This purpose of this study was to examine the spatial coding of eye movements during roll tilt relative to perceived orientations while free-floating during the microgravity phase of parabolic flight or during head tilt in normal gravity. Binocular videographic recordings obtained in darkness from six subjects allowed us to quantify the mean deviations in gaze trajectories along both horizontal and vertical coordinates relative to the aircraft and head orientations. Both variability and curvature of gaze trajectories increased during roll tilt compared to the upright position. The saccades were less accurate during parabolic flight compared to measurements obtained in normal gravity. The trajectories of saccades along perceived horizontal orientations tended to deviate in the same direction as the head tilt, while the deviations in gaze trajectories along the perceived vertical orientations deviated in the opposite direction relative to the head tilt. Although subjects were instructed to look off in the distance while performing the eye movements, fixation distance varied with vertical gaze direction independent of whether the saccades were made along perceived aircraft or head orientations. This coupling of horizontal vergence with vertical gaze is in a consistent direction with the vertical slant of the horopter. The increased errors in gaze trajectories along both perceived orientations during microgravity can be attributed to the otolith's role in spatial coding of eye movements

Imaging Complex Structure in Shallow Seismic-reflection Data Using Prestack Depth Migration

Prestack depth migration (PSDM) analysis has the potential to significantly improve the accuracy of both shallow seismic reflection images and the measured velocity distributions. In a study designed to image faults in the Alvord Basin, Oregon, at depths from 25–1000 m, PSDM produced a detailed reflection image over the full target depth range. In contrast, poststack time migration produced significant migration artifacts in the upper 100 m that obscured reflection events and limited the structural interpretation in the shallow section. Additionally, an abrupt increase from ~2500 to \u3e3000 m/s in the PSDM velocity model constrained the interpretation of the transition from sedimentary basin fill to basement volcanic rocks. PSDM analysis revealed a complex extensional history with at least two distinct phases of basin growth and a midbasin basement high that forms the division between two major basin compartments