Conserved laws and dynamical structure of axions coupled to photons

In this work, we carry out a study of the conserved quantities and dynamical structure of the four-dimensional modified axion electrodynamics theory described by the axion-photon coupling. In the first part of the analysis, we employ the covariant phase space method to construct the conserved currents and to derive the Noether charges associated with the gauge symmetry of the theory. We further derive the improved energy–momentum tensor using the Belinfante–Rosenfeld procedure, which leads us to the expressions for the energy, momentum, and energy flux densities. Thereafter, with the help of Faddeev–Jackiw’s Hamiltonian reduction formalism, we obtain the relevant fundamental brackets structure for the dynamic variables and the functional measure for determining the quantum transition amplitude. We also confirm that modified axion electrodynamics has three physical degrees of freedom per space point. Moreover, using this symplectic framework, we yield the gauge transformations and the structure of the constraints directly from the zero-modes of the corresponding pre-symplectic matrix.

Single-domain antibody screening by isPLA-seq

Single-domain antibody (sdAb) holds the promising strategies for diverse research and translational applications. Here, we describe a method for the adaptation of the in situ proximity ligation assay (isPLA) followed by sequencing (isPLA-seq) to facilitate screening of a high-sensitive, high-throughput sdAb library for a given protein at subcellular and single-cell resolution. Based on the sequence of complementarity-determining region 3 (CDR3), the recombinant sdAb can be produced for in vitro and in vivo utilities. This method provides a general means to identify the functional measure of sdAb and its complementary epitopes and its potential applications to investigate cellular processes.

Outcome of Community-Based Early Intervention and Rehabilitation for Children with Cerebral Palsy in Rural Bangladesh: A Quasi-Experimental Study

We evaluated the outcome of a community-based early intervention and habilitation for children with cerebral palsy (CP) in Bangladesh. Children registered on the Bangladesh CP Register (BCPR) were recruited in two groups for this study: Group A received a comprehensive six-month long community-based caregiver-led intervention program at the “Shishu Shorgo” (Bengali title, which translates to ‘Children’s Heaven’) Early Intervention and Rehabilitation Centres developed to support participants from the BCPR. Group B received standard care. A quasi-experimental study was conducted. Data were obtained at baseline, at the end of the program (i.e., 6 months), and at a 12-month follow-up. Outcome measures for children included gross motor functional measure (GMFM-66), Communication Function Classification System (CFCS), and Viking Speech Scale (VSS) and, for adult caregivers, the depression, anxiety, and stress scale (DASS 21). Between October 2016 and March 2017, 156 children with CP were recruited (77 in Group A and 79 in Group B). The total score of GMFM-66, CFCS level, and VSS level significantly improved statistically in Group A (p < 0.05 for all) and deteriorated in Group B (p < 0.001, p = 0.095, p = 0.232). The intervention showed promising outcomes particularly for children with CP under five years of age. There is a need for caregiver-led community-based programs for children with CP in LMICs.

Perturbative linearization of super-Yang-Mills theories in general gauges

Supersymmetric Yang-Mills theories can be characterized by a non-local and non-linear transformation of the bosonic fields (Nicolai map) mapping the interacting functional measure to that of a free theory, such that the Jacobi determinant of the transformation equals the product of the fermionic determinants obtained by integrating out the gauginos and ghosts at least on the gauge hypersurface. While this transformation has been known so far only for the Landau gauge and to third order in the Yang-Mills coupling, we here extend the construction to a large class of (possibly non-linear and non-local) gauges, and exhibit the conditions for all statements to remain valid off the gauge hypersurface. Finally, we present explicit results to second order in the axial gauge and to fourth order in the Landau gauge.

Importance of Extra-Renal CYP24A1 Expression for Maintaining Mineral Homeostasis

Calcium homeostasis involves a complex interplay between kidneys, parathyroid glands, intestine and bone. Specifically, 1,25(OH)2D3 is a key calciotropic hormone which stimulates intestinal calcium absorption. A growing body of evidence suggests that circulating levels of 1,25(OH)2D3 depend not only on its synthesis under the action of PTH in the kidneys, but also its catabolism by 24-hydroxylase, herein referred to as CYP24A1. The clinical importance of CYP24A1 has been demonstrated by human loss-of-function mutations, which lead to severe hypercalcemia due to exaggerated levels of 1,25(OH)2D3. Despite its growing importance, little is known about its tissue-specific contributions to normal vitamin D metabolism. To explore the physiology of CYP24A1 and delineate renal-specific effects of CYP24A1 in calcium metabolism, we generated a mouse with constitutive kidney-specific deletion of Cyp24a1 (Six2Cre-Cyp24flox). Six2 marks the nephron progenitor population throughout nephrogenesis. We hypothesized that hypercalcemia as seen in CYP24A1 inactivating mutations is related to lack of both renal and extrarenal expression, and that renal deletion does not lead to severe hypercalcemia. To confirm Cyp24a1 deletion, we measured mRNA expression in the kidney using qPCR and RNA in situ hybridization. All mice were fed a standard commercial rodent diet and followed longitudinally for five months with interval calcium measurements. At time of termination, serum PTH levels were measured along with vitamin D-dependent calcium transporters as a functional measure of 1,25(OH)2D3 action. Cyp24a1 expression was significantly knocked down in total kidneys from Six2Cre-Cyp24flox mice as compared to intestinal expression suggesting successful gene deletion. Compared to age-matched wildtype controls, Six2Cre-Cyp24flox mice were mildly but persistently hypercalcemic (diff between means= 0.46 mg/dL, p-value: 0.03, n=8 per group). As expected, 1,25D-dependent calcium transporters in the kidney (Calb1, Trpv5, Slc8a1, Atp2b1) and intestine (Trpv6, s100g) were all increased, consistent with increased systemic 1,25(OH)2D3 activity. PTH levels were appropriately suppressed in the Six2Cre-Cyp24flox mice (diff between means=83 pg/mL, p-value 0.2, n=9 control, n=3 exp) as were renal cyp27b1 mRNA expression. These data suggest that renal CYP24A1 is important for systemic 1,25(OH)2D3 regulation, but the lack of severe hypercalcemia supports critical contributions of extra-renal CYP24A1.

844 The Frequency of Formal Audiological Assessment in Patients with Diagnosed Vestibular Schwannomas – A Single Centre audit

Introduction Patients with vestibular schwannomas (VS) must have formal audiology during their workup, according to multiple national guidelines (including NICE). Method This retrospective study sought to audit the percentage of VS cases undergoing formal audiometry at a tertiary neurosurgical centre. An illustrative sample was selected randomly from local databases (2006-2019). Data collected included audiometry types (speech discrimination [SD], pure tone audiometry [PTA]), management pathway (surgery, radiotherapy or conservative) and symptom profile. Results 200 cases were assessed, 7 were excluded (private patients, patients referred but not formally seen). Of the 193 cases included, 186 (96.4%) had ≥1 Pure Tone assessment [PTA], with 135 (70%) also tested on Speech Discrimination [SD]. The surgical cohort had the highest audiometry rates at 38/38, followed by 116/121 (96%) for surveillance and 32/34 (94%) for radiotherapy subgroups. Reasons for no audiology were: profound hearing loss at presentation (2/7), audiometry at local centres (4/7) and patient compliance (1/7). Conclusions Our service is highly compliant (96.4%), consistent across management categories. The rate of SD (70%), a functional measure of hearing impairment, can be improved. Monitoring surgical outcomes via formal audiometry should be standard, particularly surgical approaches that preserve hearing are chosen. Follow-up audiometry regimes can be standardized for those on surveillance pathways.

Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS

Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease accompanied by muscular fatigue and pain. A functional measure to assess muscle fatigability of ME/CFS patients is, however, not established in clinical routine. The aim of this study is to evaluate by assessing repeat maximum handgrip strength (HGS), muscle fatigability as a diagnostic tool and its correlation with clinical parameters. Methods We assessed the HGS of 105 patients with ME/CFS, 18 patients with Cancer related fatigue (CRF) and 66 healthy controls (HC) using an electric dynamometer assessing maximal (Fmax) and mean force (Fmean) of ten repetitive measurements. Results were correlated with clinical parameters, creatinine kinase (CK) and lactate dehydrogenase (LDH). Further, maximum isometric quadriceps strength measurement was conducted in eight ME/CFS patients and eight HC. Results ME/CFS patients have a significantly lower Fmax and Fmean HGS compared to HC (p < 0.0001). Further, Fatigue Ratio assessing decline in strength during repeat maximal HGS measurement (Fmax/Fmean) was higher (p ≤ 0.0012). The Recovery Ratio after an identical second testing 60 min later was significantly lower in ME/CFS compared to HC (Fmean2/Fmean1; p ≤ 0.0020). Lower HGS parameters correlated with severity of disease, post-exertional malaise and muscle pain and with higher CK and LDH levels after exertion. Conclusion Repeat HGS assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.

Euclidean path integrals and quantum mechanics (QM)

Functional integrals are basic tools to study first quantum mechanics (QM), and quantum field theory (QFT). The path integral formulation of QM is well suited to the study of systems with an arbitrary number of degrees of freedom. It makes a smooth transition between nonrelativistic QM and QFT possible. The Euclidean functional integral also emphasizes the deep connection between QFT and the statistical physics of systems with short-range interactions near a continuous phase transition. The path integral representation of the matrix elements of the quantum statistical operator e-β H for Hamiltonians of the simple separable form p2/2m +V(q) is derived. To the path integral corresponds a functional measure and expectation values called correlation functions, which are generalized moments, and related to quantum observables, after an analytic continuation in time. The path integral corresponding to the Euclidean action of a harmonic oscillator, to which is added a time-dependent external force, is calculated explicitly. The result is used to generate Gaussian correlation functions and also to reduce the evaluation of path integrals to perturbation theory. The path integral also provides a convenient tool to derive semi-classical approximations.

Perturbative quantum field theory (QFT): Algebraic methods

This chapter discusses systematically the algebraic properties of perturbation theory in the example of a local, relativistic scalar quantum field theory (QFT). Although only scalar fields are considered, many results can be easily generalized to relativistic fermions. The Euclidean formulation of QFT, based on the density matrix at thermal equilibrium, is studied, mainly in the simpler zero-temperature limit, where all d coordinates, Euclidean time and space, can be treated symmetrically. The discussion is based on field integrals, which define a functional measure. The corresponding expectation values of product of fields called correlation functions are analytic continuations to imaginary (Euclidean) time of the vacuum expectation values of time-ordered products of field operators. They have also an interpretation as correlation functions in some models of classical statistical physics, in continuum formulations or, at equal time, of finite temperature QFT. The field integral, corresponding to an action to which a term linear in the field coupled to an external source J has been added, defines a generating functional Z(J) of field correlation functions. The functional W(J) = ln Z(J) is the generating functional of connected correlation functions, to which contribute only connected Feynman diagrams. In a local field theory connected correlation functions, as a consequence of locality, have cluster properties. The Legendre transform Γ(φ) [N1]of W(J) is the generating functional of vertex functions. To vertex functions contribute only one-line irreducible Feynman diagrams, also called one-particle irreducible (1PI).