Osteoarthritis year in review 2023: Epidemiology & therapy.

OBJECTIVE: To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year. METHODS: Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches. RESULTS: 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors - population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences. CONCLUSIONS: Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals.

Observation of Skewed Electromagnetic Wakefields in an Asymmetric Structure Driven by Flat Electron Bunches.

Relativistic charged-particle beams that generate intense longitudinal fields in accelerating structures also inherently couple to transverse modes. The effects of this coupling may lead to beam breakup instability and thus must be countered to preserve beam quality in applications such as linear colliders. Beams with highly asymmetric transverse sizes (flat beams) have been shown to suppress the initial instability in slab-symmetric structures. However, as the coupling to transverse modes remains, this solution serves only to delay instability. In order to understand the hazards of transverse coupling in such a case, we describe here an experiment characterizing the transverse effects on a flat beam, traversing near a planar dielectric lined structure. The measurements reveal the emergence of a previously unobserved skew-quadrupolelike interaction when the beam is canted transversely, which is not present when the flat beam travels parallel to the dielectric surface. We deploy a multipole field fitting algorithm to reconstruct the projected transverse wakefields from the data. We generate the effective kick vector map using a simple two-particle theoretical model, with particle-in-cell simulations used to provide further insight for realistic particle distributions.

Phase Space Reconstruction from Accelerator Beam Measurements Using Neural Networks and Differentiable Simulations.

Characterizing the phase space distribution of particle beams in accelerators is a central part of understanding beam dynamics and improving accelerator performance. However, conventional analysis methods either use simplifying assumptions or require specialized diagnostics to infer high-dimensional (>2D) beam properties. In this Letter, we introduce a general-purpose algorithm that combines neural networks with differentiable particle tracking to efficiently reconstruct high-dimensional phase space distributions without using specialized beam diagnostics or beam manipulations. We demonstrate that our algorithm accurately reconstructs detailed 4D phase space distributions with corresponding confidence intervals in both simulation and experiment using a limited number of measurements from a single focusing quadrupole and diagnostic screen. This technique allows for the measurement of multiple correlated phase spaces simultaneously, which will enable simplified 6D phase space distribution reconstructions in the future.

Creation of a protective space between the rectum and prostate prior to prostate radiotherapy using a hydrogel spacer.

The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.

PE MIMICS: a structured approach for the emergency radiologist in the evaluation of chest pain.

Chest pain is a common reason for presentation to the emergency department. In many cases, a CTPA or CT thoracic aorta is performed during work up to assess for pulmonary embolism and aortic pathology, critical diagnoses that can be difficult to out rule clinically. However, the causes of chest pain are myriad. It is therefore crucial for the interpreting radiologist to be cognizant of other potential etiologies when interpreting these studies. The purpose of this pictorial essay is to highlight the causes of non-PE or aortic-related chest pain and provide radiologists with a structured approach to interpreting these studies, ensuring a comprehensive search strategy so that important pathologies are not missed.

Single Shot Characterization of High Transformer Ratio Wakefields in Nonlinear Plasma Acceleration.

Plasma wakefields can enable very high accelerating gradients for frontier high energy particle accelerators, in excess of 10 GeV/m. To overcome limits on single stage acceleration, specially shaped drive beams can be used in both linear and nonlinear plasma wakefield accelerators (PWFA), to increase the transformer ratio, implying that the drive beam deceleration is minimized relative to acceleration obtained in the wake. In this Letter, we report the results of a nonlinear PWFA, high transformer ratio experiment using high-charge, longitudinally asymmetric drive beams in a plasma cell. An emittance exchange process is used to generate variable drive current profiles, in conjunction with a long (multiple plasma wavelength) witness beam. The witness beam is energy modulated by the wakefield, yielding a response that contains detailed spectral information in a single-shot measurement. Using these methods, we generate a variety of beam profiles and characterize the wakefields, directly observing transformer ratios up to R=7.8. Furthermore, a spectrally based reconstruction technique, validated by 3D particle-in-cell simulations, is introduced to obtain the drive beam current profile from the decelerating wake data.

Evidence for newly generated interneurons in the basolateral amygdala of adult mice.

New neurons are continually generated from the resident populations of precursor cells in selective niches of the adult mammalian brain such as the hippocampal dentate gyrus and the olfactory bulb. However, whether such cells are present in the adult amygdala, and their neurogenic capacity, is not known. Using the neurosphere assay, we demonstrate that a small number of precursor cells, the majority of which express Achaete-scute complex homolog 1 (Ascl1), are present in the basolateral amygdala (BLA) of the adult mouse. Using neuron-specific Thy1-YFP transgenic mice, we show that YFP+ cells in BLA-derived neurospheres have a neuronal morphology, co-express the neuronal marker ßIII-tubulin, and generate action potentials, confirming their neuronal phenotype. In vivo, we demonstrate the presence of newly generated BrdU-labeled cells in the adult BLA, and show that a proportion of these cells co-express the immature neuronal marker doublecortin (DCX). Furthermore, we reveal that a significant proportion of GFP+ neurons (~23%) in the BLA are newly generated (BrdU+) in DCX-GFP mice, and using whole-cell recordings in acute slices we demonstrate that the GFP+ cells display electrophysiological properties that are characteristic of interneurons. Using retrovirus-GFP labeling as well as the Ascl1CreERT2 mouse line, we further confirm that the precursor cells within the BLA give rise to mature and functional interneurons that persist in the BLA for at least 8 weeks after their birth. Contextual fear conditioning has no effect on the number of neurospheres or BrdU-labeled cells in the BLA, but produces an increase in hippocampal cell proliferation. These results demonstrate that neurogenic precursor cells are present in the adult BLA, and generate functional interneurons, but also show that their activity is not regulated by an amygdala-dependent learning paradigm.

Neuropathic pain in end-stage hip and knee osteoarthritis: differential associations with patient-reported pain at rest and pain on activity.

OBJECTIVE: We investigated whether pain at rest and pain on activity were differentially associated with neuropathic pain scores in individuals with end-stage hip and knee OA. DESIGN: Study participants were 843 patients with hip or knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires, measures of socio-demographics, health status, medication use, neuropathic pain (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear regression models were estimated for men and women separately to examine the association between neuropathic pain scores (outcome) and study measures, entered in blocks. RESULTS: Sample mean age was 65.1 years (SD: 9.6); 57.1% were women. Mean painDETECT scores were significantly higher (P ≤Ö¹ 0.001) for women (11.2 ± 6.6 out of 38) than men (9.3 ± 7.0), with 35.6% of women and 27.7% of men meeting cut-offs for possible or likely neuropathic pain. In the final regression model for women, the coefficients for both types of pain were statistically significant, although the coefficient for pain at rest was 1.6 times greater than that for pain on activity. For men, only pain at rest was significantly associated with neuropathic pain scores. CONCLUSIONS: Findings support that possible neuropathic pain is experienced by a notable proportion of patients with end-stage hip and knee OA and is more strongly associated with pain at rest than pain on activity, particularly in men. Clinical presentation of pain at rest may warrant more thorough evaluation for potential neuropathic pain and have implications for appropriate pain management.

Observation of High Transformer Ratio of Shaped Bunch Generated by an Emittance-Exchange Beam Line.

Collinear wakefield acceleration has been long established as a method capable of generating ultrahigh acceleration gradients. Because of the success on this front, recently, more efforts have shifted towards developing methods to raise the transformer ratio (TR). This figure of merit is defined as the ratio of the peak acceleration field behind the drive bunch to the peak deceleration field inside the drive bunch. TR is always less than 2 for temporally symmetric drive bunch distributions and therefore recent efforts have focused on generating asymmetric distributions to overcome this limitation. In this Letter, we report on using the emittance-exchange method to generate a shaped drive bunch to experimentally demonstrate a TR≈5 in a dielectric wakefield accelerator.

Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex?

OBJECTIVE: We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex. DESIGN: Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested. RESULTS: Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P < 0.01; 4+ joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4 mg/l vs 9.3, P = 0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P < 0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men. CONCLUSIONS: There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation.

Precision Control of the Electron Longitudinal Bunch Shape Using an Emittance-Exchange Beam Line.

We report on the experimental generation of relativistic electron bunches with a tunable longitudinal bunch shape. A longitudinal bunch-shaping (LBS) beam line, consisting of a transverse mask followed by a transverse-to-longitudinal emittance exchange (EEX) beam line, is used to tailor the longitudinal bunch shape (or current profile) of the electron bunch. The mask shapes the bunch's horizontal profile, and the EEX beam line converts it to a corresponding longitudinal profile. The Argonne wakefield accelerator rf photoinjector delivers electron bunches into a LBS beam line to generate a variety of longitudinal bunch shapes. The quality of the longitudinal bunch shape is limited by various perturbations in the exchange process. We develop a simple method, based on the incident slope of the bunch, to significantly suppress the perturbations.

Use of antiretroviral treatment among people living with HIV in Australia between 1997 and 2012.

Current international targets aim for 90% of people diagnosed with HIV to be on antiretroviral treatment (ART). This paper aims to identify sociodemographic and attitudinal factors associated with ART non-use over time in three samples of Australian people living with HIV (PLHIV). Data for this paper were derived from an Australian cross-sectional survey of PLHIV that was repeated at three different time points: 1997, 2003, and 2012. There were approximately 1000 respondents to each survey (n = 3042 in total). The survey included approximately 250 items related broadly to health and well-being, ART use, and attitudes towards ART use. Univariate and multivariate logistic regression analyses were used. While the proportion of participants using ART increased between 1997 and 2012 (78.8-87.6%, p < .001), there was a decrease between 1997 and 2003 to 70.6% (p < .001). Factors linked to ART non-use remained steady over those 15 years. In all cohorts, people less likely to be using ART were younger and had a more recent diagnosis of HIV. In 2003 and 2012, people in full-time employment were less likely to be using ART, while those whose main source of income was a pension or social security were more likely to be using ART. Multivariate models showed that, at each time point, a belief in the health benefits of delayed ART uptake was associated with non-use. These findings suggest that there may be barriers to ART uptake that have persisted over time despite changes to clinical guidelines that now encourage early uptake.

Social support mediates the relationships between extraversion, neuroticism, and cognitive function in older adults.

OBJECTIVES: We supplement existing findings on a link between social support and cognitive function in later life by considering the role of personality as an antecedent to both, and of social support as a mediator of the link between personality and cognitive function. STUDY DESIGN: An observational cohort study. METHODS: We evaluated social support using the Lubben Social Network Scale, across 624 adults aged over 60 years, and investigated this measure as a mediator of the relationships between extraversion and neuroticism at baseline 2007-2009, and cognitive function at follow-up, 2 years later. A half-longitudinal mediation design, within a structural equation modelling framework, was used. RESULTS: There was a direct effect of extraversion, such that lower levels were related to higher scores of cognitive function. There was no significant direct effect of neuroticism on cognitive function at follow-up. Social support partially mediated the paths between both extraversion and neuroticism and cognitive function at follow-up. Decomposing the mediation effects by using social support subscales (measuring support from friends, relatives and neighbours) showed meaningful indirect effects for both predictors. CONCLUSION: Results suggest that social support may offer a target for interventions for cognitively at-risk older adults and add to the existing empirical evidence describing the link between personality and cognitive function.

Ireland's recent contribution to the radiological literature; a bibliometric analysis.

The aim of this study was to identify and analyse all articles published by Irish radiology departments in the medical literature since the year 2000. The PubMed database was searched to identify and review all articles published by radiologists based in the Republic of Ireland or Northern Ireland. Citation counts were then obtained and the top ten most cited articles were identified. There were 781 articles published during the study period. Of these, 558 (71%) were published in radiology journals and the remaining 223 (29%) were published in general medical journals. Abdominal radiology was the most represented sub-specialty (33% of all articles). There was a general trend of increased publications per year. Only 75 (9.6%) of articles were collaborative efforts by more than one radiology department. Irish radiology departments have a considerable research output and this has increased since the year 2000. More collaborative research between Irish radiology departments is encouraged.

Interaction of an Ultrarelativistic Electron Bunch Train with a W-Band Accelerating Structure: High Power and High Gradient.

Electron beam interaction with high frequency structures (beyond microwave regime) has a great impact on future high energy frontier machines. We report on the generation of multimegawatt pulsed rf power at 91 GHz in a planar metallic accelerating structure driven by an ultrarelativistic electron bunch train. This slow-wave wakefield device can also be used for high gradient acceleration of electrons with a stable rf phase and amplitude which are controlled by manipulation of the bunch train. To achieve precise control of the rf pulse properties, a two-beam wakefield interferometry method was developed in which the rf pulse, due to the interference of the wakefields from the two bunches, was measured as a function of bunch separation. Measurements of the energy change of a trailing electron bunch as a function of the bunch separation confirmed the interferometry method.

Treatment and outcomes of metastatic colorectal cancer in Australia: defining differences between public and private practice.

BACKGROUND: Prior studies have suggested improved outcomes for cancer patients managed in private centres, despite universal healthcare within Australia. AIMS: To compare patient, disease, treatment and survival data for metastatic colorectal cancer (mCRC) managed in private versus public centres. METHODS: Analysis of prospectively collected registry data for consecutive patients with mCRC managed at 16 participating centres from July 2009. RESULTS: Data for 1065 patients were examined. Age, gender and Charlson comorbidity score were similar for public and private patients. Private patients were more commonly Eastern Cooperative Oncology Group performance score 0-1 (85% vs 78%, P = 0.008), in the highest Index of Relative Socioeconomic Advantage and Disadvantage quintile (57% vs 18%, P < 0.001) or had a single metastatic site (62% vs 54%, P = 0.009). Patients treated in private were more likely to receive chemotherapy (84% vs 70%, P < 0.001), bevacizumab (59% vs 50%, P = 0.008), be treated with curative intent (37% vs 26%, P < 0.001) and undergo metastasectomy (30% vs 22%, P = 0.001). These management differences remained statistically significant after adjusting for baseline characteristics. Management in the private setting was associated with superior overall survival (median 27.9 vs 20 months, hazard ratio 0.7, 95% confidence interval: 0.57 to 0.86, P = 0.001), significant in multivariate analysis adjusting for all baseline covariates. CONCLUSIONS: Significant differences in baseline characteristics were noted for private versus public patients. However, these do not explain the higher rates of treatment delivery in the private setting, which likely contributed towards the observed survival difference. Further studies are required to determine if the increased likelihood of intervention in the private setting is driven by patient, clinician and/or institutional factors.

The health perspectives of Australian adolescents from same-sex parent families: a mixed methods study.

BACKGROUND: Research involving adolescents from same-sex parent families provides an important contribution to the evidence base on their health, well-being and the impact of stigma. To date reports on the perspectives of adolescents with same-sex attracted parents have been limited. This study aimed to describe the multidimensional experiences of physical, mental and social well-being of adolescents living in this context. METHODS: A mixed methods study of adolescents with same-sex attracted parents comprising of an adolescent-report survey of 10- to 17-year-olds and family interviews with adolescents and their parents. Data were collected in 2012 and 2013 as part of the Australian Study of Child Health in Same-Sex Families. RESULTS: The findings from qualitative interviews with seven adolescents and responses to an open-ended survey question (n = 16) suggest four themes: perceptions of normality, positive concepts of health, spheres of life (including family, friends and community) and avoiding negativity. The quantitative sample of adolescents with same-sex attracted parents (n = 35) reported higher scores than population normative data on the dimensions general health and family activities within the Child Health Questionnaire (CHQ) as well as higher on the peer problems scale on the Strengths and Difficulties Questionnaire (SDQ). Perceived stigma correlates with lower health and well-being overall. CONCLUSIONS: Positive health outcomes are informed by the ways adolescents conceptualize health and how they construct their spheres of life. Peer relationships, and community perspectives of same-sex families, inform perceived stigma and its correlation with poorer health and well-being. Although adolescents see their families as essentially normal they are negatively affected by external societal stigma.

Pyrinomonas methylaliphatogenes gen. nov., sp. nov., a novel group 4 thermophilic member of the phylum Acidobacteria from geothermal soils.

An aerobic, thermophilic, moderately acidophilic non-spore-forming bacterium, strain K22(T), was isolated from geothermally heated soil at Mount Ngauruhoe, New Zealand. On the basis of 16S rRNA gene sequence similarity, K22(T) was shown to belong to subdivision 4 of the phylum Acidobacteria and to be most closely related to 'Candidatus Chloracidobacterium thermophilum' (86 %) and Blastocatella fastidiosa (86 %). Cells stained Gram-negative and were catalase and oxidase-positive. The major fatty acids detected were iso-C15 : 0, iso-C17 : 0, iso-C19 : 0 and iso-C21 : 0 when standard lipid extraction protocols were employed. Analysis of the total cell lipid acid hydrolysate also detected membrane-spanning and ether lipids, which made up approximately 40 % of the total membrane composition. These lipids included dicarboxylic (iso-diabolic) acid and the glyceryl ether of alkyl analogues of iso-C15 : 0 and iso-diabolic acid. The G+C content of the genomic DNA was 59.6 mol% and the primary respiratory quinone was MK-8. Strain K22(T) grew at 50-69 °C with an optimum temperature of 65 °C and at pH 4.1-7.8 with an optimum growth pH of 6.5. NaCl tolerance was up to 1 % (w/v). Cells displayed a chemoheterotrophic and obligately aerobic metabolism. Cells grew on nutrient broth, alginate, arabinose, Casamino acids, glucose, lactate, formate, mannose, sodium alginate, peptone, sucrose, tryptone, xanthan, xylan, xylose and yeast extract. Nitrogen sources included nitrate, ammonium, urea, yeast extract and Casamino acids, but not dinitrogen gas. The distinct phylogenetic position and the phenotypic characteristics separate strain K22(T) from all other members of the class Acidobacteria and indicate that it represents a novel species and genus, for which the name Pyrinomonas methylaliphatogenes gen. nov., sp. nov. is proposed. The type strain of the type species is K22(T) ( = DSM 25857(T) = ICMP 18710(T)).

Bone marrow levels of 25 hydroxy vitamin D are not depressed in cases of hip fracture compared with controls.

There is little information on tissue as distinct from plasma levels of vitamin D metabolites in cases of hip fracture compared with controls. Femoral neck fractures in the elderly are associated with increased cortical remodelling and endosteal resorption, leading to regional increases in porosity and reduced cortical thickness. Vitamin D metabolites play a central role in the maintenance of normal serum calcium levels and may, through interactions with parathyroid hormone, exert an important influence on bone structure. To investigate whether hip fracture might be associated with tissue vitamin D deficiency, we have measured by radioimmunoassay the levels of 25 hydroxy vitamin D (25 (OH)D) in bone marrow samples extracted from the proximal femurs of 16 female subjects who had suffered fracture (mean age = 82.1 years, standard error (se) 1.9) and nine sex matched post mortem controls (mean age = 83.8 years, se 2.5). Twenty five (OH)D concentrations were significantly greater in the fracture cases (median = 3.7, IQR = 2.5-3.9 ng/g) than in the control group (median = 1.5, IQR = 0.9-2.3 ng/g; P = 0.0007, non-parametric Wilcoxon/Kruskal-Wallis test). It was suggested in the 1970s that bone loss and hip fracture risk in the UK were driven by vitamin D deficiency. Our results suggest that the alterations in femoral neck bone microstructure and remodelling in hip fracture cannot be assigned to the single cause of relative deficiency of vitamin D. Vitamin D deficiency or insufficiency may nevertheless increase remodelling and loss of bone tissue and contribute causally to a minority of hip fractures.