Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta

Introduction: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. Methods and analysis: Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. Ethics and dissemination: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. Trial registration number: ISRCTN15313991

Angular Conditions,Relations between Breit and Light-Front Frames, and Subleading Power Corrections

We analyze the current matrix elements in the general collinear (Breit) frames and find the relation between the ordinary (or canonical) helicity amplitudes and the light-front helicity amplitudes. Using the conservation of angular momentum, we derive a general angular condition which should be satisfied by the light-front helicity amplitudes for any spin system. In addition, we obtain the light-front parity and time-reversal relations for the light-front helicity amplitudes. Applying these relations to the spin-1 form factor analysis, we note that the general angular condition relating the five helicity amplitudes is reduced to the usual angular condition relating the four helicity amplitudes due to the light-front time-reversal condition. We make some comments on the consequences of the angular condition for the analysis of the high-$Q^2$ deuteron electromagnetic form factors, and we further apply the general angular condition to the electromagnetic transition between spin-1/2 and spin-3/2 systems and find a relation useful for the analysis of the N-$\Delta$ transition form factors. We also discuss the scaling law and the subleading power corrections in the Breit and light-front frames.Comment: 24 pages,2 figure

Sum rules and dualities for generalized parton distributions: is there a holographic principle?

To leading order approximation, the physical content of generalized parton distributions (GPDs) that is accessible in deep virtual electroproduction of photons or mesons is contained in their value on the cross-over trajectory. This trajectory separates the t-channel and s-channel dominated GPD regions. The underlying Lorentz covariance implies correspondence between these two regions through their relation to GPDs on the cross-over trajectory. This point of view leads to a family of GPD sum rules which are a quark analogue of finite energy sum rules and it guides us to a new phenomenological GPD concept. As an example, we discuss the constraints from the JLab/Hall A data on the dominant u-quark GPD H. The question arises whether GPDs are governed by some kind of holographic principle.Comment: 45 pages, 4 figures, Sect. 2 reorganized for clarity. Typos in Eq. (20) corrected. 4 new refs. Matches published versio

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity

Interface formation in InAs/AlSb and InAs/AlAs/AlSb quantum wells grown by molecular-beam epitaxy

We have used resonant Raman scattering from both longitudinal-optical phonons and interface modes to study the chemical bonding across the InAs/AlSb interface in InAs/AlSb quantum wells grown by molecular-beam epitaxy. The effusion cell shutter sequence at the interfaces was selected for the deposition of either one monolayer of InSb or two to three monolayers of AlAs. In all cases an InSb-like interface mode is observed, indicating the preferential formation of InSb interface bonds irrespective of the shutter sequence. The deposition of two or three monolayers of AlAs at the InAs/AlSb interface results in the formation of pseudoternary AlSb (ind 1-x) As (ind x) barriers rather than binary AlAs interfaces and AlSb barriers, indicating a strong exchange among the group-V atoms. Normal (AlSb on InAs) and inverted (InAs on AlSb) InAs/AlSb interfaces have also been compared, revealing a much stronger InSb-like interface mode for the growth of AlSb on InAs than for the case of InAs grown on AlSb

Carrier capture and escape times in In(0,35)Ga(0,65)As-GaAs multiquantum-well lasers determined from high-frequency electrical impedance measurements

We present experimental results on the high- frequency electrical impedance of In(0.35)Ga(0.65)As-GaAS multiquantum-well lasers with varied p-doping levels in the active region. The analysis of the data, using a simple three rate equation model, provides information about the dynamical time constants (the carrier lifetime, the effective carrier capture and escape times) under the laser operation conditions. The addition of p-doping increases the carrier escape time at threshold from 0.7 ns, extracted for the undoped devices, up to a value higher than 2 ns for the p-doped lasers. The effective capture time is estimated to be between 2 and 5 ps

Vertically compact 15 GHz GaAs/AlGaAs multiple quantum well laser grown by molecular beam epitaxy.

A GaAs/AlxGa1-xAs multiple quantum well laser with an electrical modulation bandwidth exceeding 15 GHz has been fabricated. Optimised design of the waveguide, including development of high Al mole fraction (x equal 0.8) cladding layers, together with a coplanar electrode geometry, has resulted in a vertically compact laser structure suitable for integration

MBE growth optimization of InyGa1-yAs/GaAs multiple quantum well structures.

We have grown pseudomorphic InsubyGasub1-yAs multiple quantum wells (MQWs) with y is equal 0.20 and y is equal 0.35, using four MBE and one migration-enhanced epitaxy (MEE) growth conditions. MQWs grown by MBE at 450 degree C had the narrowest photoluminescence (PL) linewidths and largest PL intensities. MQWs grown at 480 degree C had comparable integrated PL intensities, but larger linewidths. The growth stops in MQWs grown at 480 degree C improved the PL linewidths. The MEE MQWs had large PL linewidths and low PL intensities. High depth-resolution secondary ion mass spectrometry (SIMS) analysis was shown to be very sensitive to interface roughness. The lateral homogeneity of the Insub0.35Gasub0.65As MQWs was investigated with scanning cathodoluminescence (CL) imaging. The SIMS and CL data corroborate the PL results, showing that lower temperatures and growth stops reduce interface roughness