An “orientation sphere” visualization for examining animal head movements

Animal behavior is elicited, in part, in response to external conditions, but understanding how animals perceive the environment and make the decisions that bring about these behavioral responses is challenging.Animal heads often move during specific behaviors and, additionally, typically have sensory systems (notably vision, smell, and hearing) sampling in defined arcs (normally to the front of their heads). As such, head‐mounted electronic sensors consisting of accelerometers and magnetometers, which can be used to determine the movement and directionality of animal heads (where head “movement” is defined here as changes in heading [azimuth] and/or pitch [elevation angle]), can potentially provide information both on behaviors in general and also clarify which parts of the environment the animals might be prioritizing (“environmental framing”).We propose a new approach to visualize the data of such head‐mounted tags that combines the instantaneous outputs of head heading and pitch in a single intuitive spherical plot. This sphere has magnetic heading denoted by “longitude” position and head pitch by “latitude” on this “orientation sphere” (O‐sphere).We construct the O‐sphere for the head rotations of a number of vertebrates with contrasting body shape and ecology (oryx, sheep, tortoises, and turtles), illustrating various behaviors, including foraging, walking, and environmental scanning. We also propose correcting head orientations for body orientations to highlight specific heading‐independent head rotation, and propose the derivation of O‐sphere‐metrics, such as angular speed across the sphere. This should help identify the functions of various head behaviors.Visualizations of the O‐sphere provide an intuitive representation of animal behavior manifest via head orientation and rotation. This has ramifications for quantifying and understanding behaviors ranging from navigation through vigilance to feeding and, when used in tandem with body movement, should provide an important link between perception of the environment and response to it in free‐ranging animals

Measurement of Muscular Activity Associated With Peristalsis in the Human Gut Using Fiber Bragg Grating Arrays

Author version made available under Publisher copyright policy.Diagnostic catheters based on fibre Bragg gratings (FBG’s) are proving to be highly effective for measurement of the muscular activity associated with peristalsis in the human gut. The primary muscular contractions that generate peristalsis are circumferential in nature; however, it has long been known that there is also a component of longitudinal contractility present, acting in harmony with the circumferential component to improve the overall efficiency of material movement. We report on the development of, and latest results from, catheter based sensors capable of detecting both forms of muscular activity. While detection of the circumferential contractions has been possible using solid state, hydraulic, and pneumatic sensor arrays in the oesophagus and anorectum, FBG based devices allow access into the complex and convoluted regions of the gut below the stomach. We report early results from FBG catheters used during trials of novel therapies in patients with both slow transit constipation and faecal incontinence. In addition, there have been relatively few reports on the measurement or inference of longitudinal contractions in humans. This is due to the lack of a viable recording technique suitable for real-time in-vivo measurement of this type of activity over extended lengths of the gut. We report preliminary data on the detection of longitudinal motion in lengths of excised mammalian colon using an FBG technique that should be viable for similar detection in humans. The longitudinal sensors have been combined with pressure sensing elements to form a composite catheter that allows the relative phase between the two components to be detected. The output of both types of catheter has been validated using digital video mapping in an ex-vivo animal preparation using lengths of rabbit ileum

Dupilumab provides favourable long‐term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled, severe atopic dermatitis: results from an open‐label phase IIa study and subsequent phase III open‐label extension study

Background Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16‐week, randomized, placebo‐controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)‐4/IL‐13 signalling, significantly improved signs and symptoms with acceptable safety; longer‐term safety and efficacy data are lacking. Objectives To report the pharmacokinetic profile and long‐term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. Methods Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study and subsequent open‐label extension (OLE) study. Patients received single‐dose dupilumab 2 or 4 mg kg−1 followed by 8‐week pharmacokinetic sampling, then 2 or 4 mg kg−1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration–time profile and treatment‐emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP‐NRS) score. Results Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target‐mediated pharmacokinetics characterized dupilumab concentrations (week 24–48 mean serum concentrations: 2 mg kg−1, 61–77 mg L−1; 4 mg kg−1, 143–181 mg L−1). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg−1, 47%; 4 mg kg−1, 56%) and AD exacerbation (29% and 13%, respectively). Single‐dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP‐NRS improved by −37%/−33% and −17%/−20% at week 2 (phase IIa) and −92%/−84% and −70%/−58% at week 52 (OLE), respectively. Conclusions These safety and efficacy results support the use of dupilumab as a continuous long‐term treatment for children aged ≥ 6 to < 12 years with severe AD

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Pelvic Organ Prolapse (POP) is a major clinical burden affecting 25% of women, with vaginal delivery a major contributing factor. We hypothesised that increasing parity weakens the vagina by altering the extracellular matrix proteins and smooth muscle thereby leading to POP vulnerability. We used a modified POP-quantification (POP-Q) system and a novel pressure sensor to measure vaginal wall weakness in nulliparous, primiparous and multiparous ewes. These measurements were correlated with histological, biochemical and biomechanical properties of the ovine vagina. Primiparous and multiparous ewes had greater displacement of vaginal tissue compared to nulliparous at points Aa, Ap and Ba and lower pressure sensor measurements at points equivalent to Ap and Ba. Vaginal wall muscularis of multiparous ewes was thinner than nulliparous and had greater elastic fibre content. Collagen content was lower in primiparous than nulliparous ewes, but collagen organisation did not differ. Biomechanically, multiparous vaginal tissue was weaker and less stiff than nulliparous. Parity had a significant impact on the structure and function of the ovine vaginal wall, as the multiparous vaginal wall was weaker and had a thinner muscularis than nulliparous ewes. This correlated with “POP-Q” and pressure sensor measurements showing greater tissue laxity in multiparous compared to nulliparous ewes

The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

Clinical Outcome and Underlying Genetic Cause of Functional Terminal Complement Pathway Deficiencies in a Multicenter UK Cohort.

Background Terminal complement pathway deficiencies often present with severe and recurrent infections. There is a lack of good-quality data on these rare conditions. This study investigated the clinical outcome and genetic variation in a large UK multi-center cohort with primary and secondary terminal complement deficiencies. Methods Clinicians from seven UK centers provided anonymised demographic, clinical, and laboratory data on patients with terminal complement deficiencies, which were collated and analysed. Results Forty patients, median age 19 (range 3–62) years, were identified with terminal complement deficiencies. Ten (62%) of 16 patients with low serum C5 concentrations had underlying pathogenic CFH or CFI gene variants. Two-thirds were from consanguineous Asian families, and 80% had an affected family member. The median age of the first infection was 9 years. Forty-three percent suffered meningococcal serotype B and 43% serotype Y infections. Nine (22%) were treated in intensive care for meningococcal septicaemia. Two patients had died, one from intercurrent COVID-19. Twenty-one (52%) were asymptomatic and diagnosed based on family history. All but one patient had received booster meningococcal vaccines and 70% were taking prophylactic antibiotics. Discussion The genetic etiology and clinical course of patients with primary and secondary terminal complement deficiency are variable. Patients with low antigenic C5 concentrations require genetic testing, as the low level may reflect consumption secondary to regulatory defects in the pathway. Screening of siblings is important. Only half of the patients develop septicaemia, but all should have a clear management plan

Surveillance and control of meningococcal disease in the COVID-19 era: A Global Meningococcal Initiative review

RevisiónThis review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes.Medical writing support was funded by Sanofi Pasteur.S

Novel STAT1 Alleles in Otherwise Healthy Patients with Mycobacterial Disease

The transcription factor signal transducer and activator of transcription-1 (STAT1) plays a key role in immunity against mycobacterial and viral infections. Here, we characterize three human STAT1 germline alleles from otherwise healthy patients with mycobacterial disease. The previously reported L706S, like the novel Q463H and E320Q alleles, are intrinsically deleterious for both interferon gamma (IFNG)–induced gamma-activating factor–mediated immunity and interferon alpha (IFNA)–induced interferon-stimulated genes factor 3–mediated immunity, as shown in STAT1-deficient cells transfected with the corresponding alleles. Their phenotypic effects are however mediated by different molecular mechanisms, L706S affecting STAT1 phosphorylation and Q463H and E320Q affecting STAT1 DNA-binding activity. Heterozygous patients display specifically impaired IFNG-induced gamma-activating factor–mediated immunity, resulting in susceptibility to mycobacteria. Indeed, IFNA-induced interferon-stimulated genes factor 3–mediated immunity is not affected, and these patients are not particularly susceptible to viral disease, unlike patients homozygous for other, equally deleterious STAT1 mutations recessive for both phenotypes. The three STAT1 alleles are therefore dominant for IFNG-mediated antimycobacterial immunity but recessive for IFNA-mediated antiviral immunity at the cellular and clinical levels. These STAT1 alleles define two forms of dominant STAT1 deficiency, depending on whether the mutations impair STAT1 phosphorylation or DNA binding

Dupilumab Treatment Leads to Rapid and Consistent Improvement of Atopic Dermatitis in All Anatomical Regions in Patients Aged 6 Months to 5 Years

Introduction: Atopic dermatitis (AD) is heterogeneous in distribution pattern and clinical features. This analysis assessed the effect of dupilumab on the extent and severity of AD across various signs (erythema, edema/papulation, excoriation, lichenification) in different anatomical regions (head and neck, trunk, upper extremities, lower extremities) in patients aged 6 months to 5 years. Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo with concomitant low-potency topical corticosteroids (TCS) every 4 weeks for 16 weeks. Changes in AD signs across anatomical regions were assessed using unweighted Eczema Area and Severity Index (EASI) body region scores. Results: Overall, 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). A significant improvement in least squares mean EASI area score was seen by week 2 in all four anatomical regions (P < 0.0001 for dupilumab vs. placebo) and sustained throughout treatment. Least squares mean EASI sign scores in erythema, excoriations, and infiltration/papulation showed significant improvement by week 2 in all regions (P < 0.001), while lichenification showed significant improvement in all regions by week 4 (P < 0.001). Conclusion: Dupilumab use with concomitant low-potency TCS treatment resulted in rapid and consistent improvement in AD signs in all anatomical regions, in patients aged 6 months to 5 years with moderate-to-severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03346434 Part B

Laboratory safety from a randomized 16-week phase III study of dupilumab in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Background and Objective: Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab. Methods: In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided. Results: No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal. Conclusions: These results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening. Clinical Trial Registration: ClinicalTrials.gov: NCT03346434, part