Lived experiences of informal caregivers of people with chronic musculoskeletal pain: a systematic review and meta-ethnography

BACKGROUND: People with chronic pain often seek support from friends and family for everyday tasks. These individuals are termed informal caregivers. There remains uncertainty regarding the lived experiences of these people who care for individuals with chronic musculoskeletal pain. The aim of this paper is to synthase the evidence on the lived experiences of informal caregivers providing care to people with chronic musculoskeletal pain. METHODS: A systematic literature review was undertaken of published and unpublished literature databases including: EMBASE, MEDLINE, CINAHL, PubMed, the WHO International Clinical Trial Registry and ClinicalTrials.gov registry (to September 2019). Qualitative studies exploring the lived experiences of informal caregivers of people with chronic musculoskeletal pain were included. Data were synthesised using a meta-ethnography approach. Evidence was evaluated using the Critical Appraisal Skills Programme (CASP) qualitative appraisal tool. RESULTS: From 534 citations, 10 studies were eligible (360 participants: 171 informal caregivers of 189 care recipients). The evidence was moderate quality. Seven themes arose: the relationship of caregivers to healthcare professionals, role reversal with care recipients; acting the confidant to the care recipient; a constant burden in caregiving; legitimising care recipient’s condition; knowledge and skills to provide caregiving; and the perception of other family members and wider-society to the caregiver/care recipient dyad. CONCLUSIONS: The lived experiences of caregivers of people with chronic musculoskeletal pain is complex and dynamic. There is an inter-connected relationship between caregivers, care recipients and healthcare professionals. Exploring how these experiences can be modified to improve a caregiving dyad’s lived experience is now warranted

Linear Paul trap design for an optical clock with Coulomb crystals

We report on the design of a segmented linear Paul trap for optical clock applications using trapped ion Coulomb crystals. For an optical clock with an improved short-term stability and a fractional frequency uncertainty of 10^-18, we propose 115In+ ions sympathetically cooled by 172Yb+. We discuss the systematic frequency shifts of such a frequency standard. In particular, we elaborate on high precision calculations of the electric radiofrequency field of the ion trap using the finite element method. These calculations are used to find a scalable design with minimized excess micromotion of the ions at a level at which the corresponding second- order Doppler shift contributes less than 10^-18 to the relative uncertainty of the frequency standard

Multi-Phase Sputtered TiO2-Induced Current–Voltage Distortion in Sb2Se3 Solar Cells

Despite the recent success of CdS/Sb2Se3 heterojunction devices, cadmium toxicity, parasitic absorption from the relatively narrow CdS band gap (2.4 eV) and multiple reports of inter-diffusion at the interface forming Cd(S,Se) and Sb2(S,Se)3 phases, present significant limitations to this device architecture. Among the options for alternative partner layers in antimony chalcogenide solar cells, the wide band gap, non-toxic titanium dioxide (TiO2) has demonstrated the most promise. It is generally accepted that the anatase phase of the polymorphic TiO2 is preferred, although there is currently an absence of analysis with regard to phase influence on device performance. This work reports approaches to distinguish between TiO2 phases using both surface and bulk characterization methods. A device fabricated with a radio frequency (RF) magnetron sputtered rutile-TiO2 window layer (FTO/TiO2/Sb2Se3/P3HT/Au) achieved an efficiency of 6.88% and near-record short–circuit current density (Jsc) of 32.44 mA cm−2, which is comparable to established solution based TiO2 fabrication methods that produced a highly anatase-TiO2 partner layer and a 6.91% efficiency device. The sputtered method introduces reproducibility challenges via the enhancement of interfacial charge barriers in multi-phase TiO2 films with a rutile surface and anatase bulk. This is shown to introduce severe S-shaped current–voltage (J–V) distortion and a drastic fill–factor (FF reduction in these devices

Stein's method on Wiener chaos

We combine Malliavin calculus with Stein's method, in order to derive explicit bounds in the Gaussian and Gamma approximations of random variables in a fixed Wiener chaos of a general Gaussian process. We also prove results concerning random variables admitting a possibly infinite Wiener chaotic decomposition. Our approach generalizes, refines and unifies the central and non-central limit theorems for multiple Wiener-It\^o integrals recently proved (in several papers, from 2005 to 2007) by Nourdin, Nualart, Ortiz-Latorre, Peccati and Tudor. We apply our techniques to prove Berry-Ess\'een bounds in the Breuer-Major CLT for subordinated functionals of fractional Brownian motion. By using the well-known Mehler's formula for Ornstein-Uhlenbeck semigroups, we also recover a technical result recently proved by Chatterjee, concerning the Gaussian approximation of functionals of finite-dimensional Gaussian vectors.Comment: 39 pages; Two sections added; To appear in PTR

Suppression of FOXM1 Sensitizes Human Cancer Cells to Cell Death Induced by DNA-Damage

Irradiation and DNA-damaging chemotherapeutic agents are commonly used in anticancer treatments. Following DNA damage FOXM1 protein levels are often elevated. In this study, we sought to investigate the potential role of FOXM1 in programmed cell death induced by DNA-damage. Human cancer cells after FOXM1 suppression were subjected to doxorubicin or γ-irradiation treatment. Our findings indicate that FOXM1 downregulation by stable or transient knockdown using RNAi or by treatment with proteasome inhibitors that target FOXM1 strongly sensitized human cancer cells of different origin to DNA-damage-induced apoptosis. We showed that FOXM1 suppresses the activation of pro-apoptotic JNK and positively regulates anti-apoptotic Bcl-2, suggesting that JNK activation and Bcl-2 down-regulation could mediate sensitivity to DNA-damaging agent-induced apoptosis after targeting FOXM1. Since FOXM1 is widely expressed in human cancers, our data further support the fact that it is a valid target for combinatorial anticancer therapy

Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy

Natalizumab is an approved medication for highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of this drug. Here, we describe pathological and radiological characteristics of immune reconstitution inflammatory syndrome (IRIS), which occurs in natalizumab-associated PML after the cessation of therapy, and we differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS patients with natalizumab-associated PML were analyzed and their histology compared with non-MS PML. Histology showed an extensive CD8-dominated T cell infiltrate and numerous macrophages within lesions, and in nondemyelinated white and grey matter, in four out of five cases. Few or no virally infected cells were found. This was indicative of IRIS as known from HIV patients with PML. Outstandingly high numbers of plasma cells were present as compared to non-MS PML and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions with a band-like or speckled contrast enhancement either at the lesion edge or within lesions. Only the fifth patient showed typical PML pathology, with low inflammation and high numbers of virally infected cells. This patient showed a similar interval between drug withdrawal and biopsy (3.5 months) to the rest of the cohort (range 2.5–4 months). MRI could not differentiate between PML-associated IRIS and ongoing PML. We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML–IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML