The prevalence of chronic pain in children and adolescents: a systematic review update and meta-analysis.

ABSTRACT: Chronic pain, defined as persistent or recurring pain or pain lasting longer than 3 months, is a common childhood problem. The objective of this study was to conduct an updated systematic review and meta-analysis on the prevalence of chronic pain (ie, overall, headache, abdominal pain, back pain, musculoskeletal pain, multisite/general pain, and other) in children and adolescents. EMBASE, PubMed, CINAHL, and PsycINFO were searched for publications between January 1, 2009, and June 30, 2023. Studies reporting population-based estimates of chronic nondisease related pain prevalence in children or adolescents (age ≤ 19 years) were included. Two independent reviewers screened articles based on a priori protocol. One hundred nineteen studies with a total of 1,043,878 children (52.0% female, mean age 13.4 years [SD 2.4]) were included. Seventy different countries were represented, with the highest number of data points of prevalence estimates coming from Finland and Germany (n = 19 each, 4.3%). The overall prevalence of chronic pain in children and adolescents was 20.8%, with the highest prevalence for headache and musculoskeletal pain (25.7%). Overall, and for all types of pain except for back pain and musculoskeletal pain, there were significant differences in the prevalence between boys and girls, with girls having a higher prevalence of pain. There was high heterogeneity (I 2 99.9%). Overall risk of bias was low to moderate. In summary, approximately 1 in 5 children and adolescents experience chronic pain and prevalence varies by pain type; for most types, there is higher pain prevalence among girls than among boys. Findings echo and expand upon the systematic review conducted in 2011.

Meiosis through three centuries.

Meiosis is the specialized cellular program that underlies gamete formation for sexual reproduction. It is therefore not only interesting but also a fundamentally important subject for investigation. An especially attractive feature of this program is that many of the processes of special interest involve organized chromosomes, thus providing the possibility to see chromosomes "in action". Analysis of meiosis has also proven to be useful in discovering and understanding processes that are universal to all chromosomal programs. Here we provide an overview of the different historical moments when the gap between observation and understanding of mechanisms and/or roles for the new discovered molecules was bridged. This review reflects also the synergy of thinking and discussion among our three laboratories during the past several decades.

Future climatically suitable areas for bats in South Asia.

Climate change majorly impacts biodiversity in diverse regions across the world, including South Asia, a megadiverse area with heterogeneous climatic and vegetation regions. However, climate impacts on bats in this region are not well-studied, and it is unclear whether climate effects will follow patterns predicted in other regions. We address this by assessing projected near-future changes in climatically suitable areas for 110 bat species from South Asia. We used ensemble ecological niche modelling with four algorithms (random forests, artificial neural networks, multivariate adaptive regression splines and maximum entropy) to define climatically suitable areas under current conditions (1970-2000). We then extrapolated near future (2041-2060) suitable areas under four projected scenarios (combining two global climate models and two shared socioeconomic pathways, SSP2: middle-of-the-road and SSP5: fossil-fuelled development). Projected future changes in suitable areas varied across species, with most species predicted to retain most of the current area or lose small amounts. When shifts occurred due to projected climate change, new areas were generally northward of current suitable areas. Suitability hotspots, defined as regions suitable for >30% of species, were generally predicted to become smaller and more fragmented. Overall, climate change in the near future may not lead to dramatic shifts in the distribution of bat species in South Asia, but local hotspots of biodiversity may be lost. Our results offer insight into climate change effects in less studied areas and can inform conservation planning, motivating reappraisals of conservation priorities and strategies for bats in South Asia.

An Optimization Approach for Creating Application-specific Ultrasound Speckle Tracking Algorithms.

OBJECTIVE: Ultrasound speckle tracking enables in vivo measurement of soft tissue deformation or strain, providing a non-invasive diagnostic tool to quantify tissue health. However, adoption into new fields is challenging since algorithms need to be tuned with gold-standard reference data that are expensive or impractical to acquire. Here, we present a novel optimization approach that only requires repeated measurements, which can be acquired for new applications where reference data might not be readily available or difficult to get hold of. METHODS: Soft tissue motion was captured using ultrasound for the medial collateral ligament (MCL) of three quasi-statically loaded porcine stifle joints, and medial ligamentous structures of a dynamically loaded human cadaveric knee joint. Using a training subset, custom speckle tracking algorithms were created for the porcine and human ligaments using surrogate optimization, which aimed to maximize repeatability by minimizing the normalized standard deviation of calculated strain maps for repeat measurements. An unseen test subset was then used to validate the tuned algorithms by comparing the ultrasound strains to digital image correlation (DIC) surface strains (porcine specimens) and length change values of the optically tracked ligament attachments (human specimens). RESULTS: After 1500 iterations, the optimization routine based on the porcine and human training data converged to similar values of normalized standard deviations of repeat strain maps (porcine: 0.19, human: 0.26). Ultrasound strains calculated for the independent test sets using the tuned algorithms closely matched the DIC measurements for the porcine quasi-static measurements (R > 0.99, RMSE < 0.59%) and the length change between the tracked ligament attachments for the dynamic human dataset (RMSE < 6.28%). Furthermore, strains in the medial ligamentous structures of the human specimen during flexion showed a strong correlation with anterior/posterior position on the ligaments (R > 0.91). CONCLUSION: Adjusting ultrasound speckle tracking algorithms using an optimization routine based on repeatability led to robust and reliable results with low RMSE for the medial ligamentous structures of the knee. This tool may be equally beneficial in other soft-tissue displacement or strain measurement applications and can assist in the development of novel ultrasonic diagnostic tools to assess soft tissue biomechanics.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

Streptococcus zooepidemicus in dogs: Exploring a canine pathogen through multilocus sequence typing.

Streptococcus equi. subsp. zooepidemicus (S. zooepidemicus) associated diseases in dogs have emerged as a significant concern over recent decades. S. zooepidemicus occurs sporadically in dog populations globally, with increased prevalence in shelters/kennels. This study used multilocus sequence typing (MLST) of 149 independent canine S. zooepidemicus isolates to assess associations between sequence type and breed, country of origin, disease severity, sampling type, year, and behaviour within an outbreak. No clear associations for breed, country, sampling type and year were determined in this study. ST-10 and 123 strains were present within all disease categories, from no clinical signs to severe disease. Assessment of S. zooepidemicus infection in 3 UK outbreaks at the same location found ST-10, 18, 123 strains, and a ST-173 strain in a US outbreak, were associated with haemorrhagic pneumonia and persisted in kennelled populations over time. The ST-173 clonal complex has been noted to have severe virulence capabilities in dogs and other species. S. zooepidemicus seems to thrive in environments with a high risk of transmissibility, overcrowding, stress and naïve populations, particularly for those in shelters/kennels. MLST alone cannot determine the virulence phenotype of S. zooepidemicus in dogs. However, a level of conservancy and diversity within ST allelic loci aids the opportunity to cause severe disease in dogs. Thus, further research into whole genome sequencing and characterising the virulence factors of S. zooepidemicus is warranted in dogs.

An ELISA Using Synthetic Mycolic Acid-Based Antigens with DIVA Potential for Diagnosing Johne's Disease in Cattle.

THE PROBLEM: Ante-mortem diagnosis of Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is normally achieved through faecal culture, PCR, or serological tests, but agreement as to which samples are positive for Johne's disease is often poor and sensitivities are low, particularly in early-stage infections. The potential solution: Mycobacterial cells contain very complex characteristic mixtures of mycolic acid derivatives that elicit antibodies during infection; this has been used to detect infections in humans. Here, we explore its application in providing an assay differentiating infected from vaccinated animals (DIVA assay) for Johne's disease in cattle. METHOD: Antibody responses to different classes of mycolic acid derivatives were measured using ELISA for serum from cattle positive for MAP by both faecal PCR and commercial serum ELISA, or just by PCR, and from animals from herds with no history of Johne's disease, bovine tuberculosis reactors, BCG-vaccinated, BCG-vaccinated and M. bovis-infected, and Gudair-vaccinated animals. RESULTS: The best-performing antigens, ZAM295 and ST123-the latter a molecule present in the cells of MAP but not of Mycobacterium bovis-achieved a sensitivity of 75% and 62.5%, respectively, for serum from animals positive by both faecal PCR and a commercial MAP serum ELISA, at a specificity of 94% compared to 80 no-history negatives. Combining the results of separate assays with two antigens (ST123 and JRRR121) increased the sensitivity/specificity to 75/97.5%. At the same cut-offs, animals vaccinated with Gudair or BCG vaccines and bTB reactors showed a similar specificity. The specificity in BCG-vaccinated but M. bovis-infected animals dropped to 85%. Combining the results of two antigens gave a sensitivity/specificity of 37.5/97.5% for the full set of 80 PCR-positive samples, detecting 30 positives compared 16 for IDEXX. CONCLUSION: Serum ELISA using synthetic lipids distinguishes effectively between MAP-negative cattle samples and those positive by both PCR and a commercial MAP serodiagnostic, without interference by Gudair or BCG vaccination. It identified almost twice as many PCR positives as the commercial serodiagnostic, offering the possibility of earlier detection of infection.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems1-4. These galaxies transitioned rapidly between starburst episodes and phases of suppressed star formation, potentially even causing temporary quiescence-so-called mini-quenching events5,6. However, the regime of star-formation burstiness is observationally highly unconstrained. Directly observing mini-quenched galaxies in the primordial Universe is therefore of utmost importance to constrain models of galaxy formation and transformation7,8. Early quenched galaxies have been identified out to redshift z < 5 (refs. 9-12) and these are all found to be massive (M⋆ > 1010 M⊙) and relatively old. Here we report a (mini-)quenched galaxy at z = 7.3, when the Universe was only 700 Myr old. The JWST/NIRSpec spectrum is very blue (U-V = 0.16 ± 0.03 mag) but exhibits a Balmer break and no nebular emission lines. The galaxy experienced a short starburst followed by rapid quenching; its stellar mass (4-6 × 108 M⊙) falls in a range that is sensitive to various feedback mechanisms, which can result in perhaps only temporary quenching.

Refixation of the anterior cruciate ligament: A biomechanical analysis of suture techniques in a porcine model.

Purpose: Refixation of acute anterior cruciate ligament (ACL) tears represents an increasingly popular treatment option. Systematic evaluations of various suture technique parameters are still pending. We therefore aimed to evaluate the mechanical pull-out outcomes of various suture methods for optimization of ACL refixation. Methods: Sixty fresh knees from mature domestic pigs were dissected and the femoral attachment of the ACL was peeled off. The 60 knees were divided in 10 groups and sutured as follows: (A) one suture (1, 2, 4 and 6 passes), (B) two sutures (2, 4 and 6 passes each; sutures knotted together as a loop) and (C) two sutures (2, 4 and 6 passes each, sutures knotted separately). The pull-out test was conducted using a validated electrodynamic testing machine. First occurrence of failure, maximum pull-out load and stiffness were measured. Suture failure was defined as pull-out of the ACL. Results: Two-point fixation, using two sutures, with at least two passes, showed the most favourable biomechanical stability. The maximum pull-out load was significantly higher with two sutures (529.5 N) used compared to one (310.4 N), p < 0.001. No significant differences were found for maximum pull-out loads between two-point fixation versus one-point fixation but stiffness was significantly higher with two-point fixation (107.4 N/mm vs. 79.4 N/mm, p < 0.001). More passes resulted in higher maximum pull-out loads. Conclusion: The results suggest using two independent sutures, refixed separately and at least two suture passes, is appropriate for ACL refixation. More suture passes provide additional strength but are technically challenging to achieve during surgery. Level of Evidence: Level IV.

The worldwide prevalence of psoriatic arthritis-a systematic review and meta-analysis.

OBJECTIVES: Previous attempts to pool prevalence studies in PsA have failed to take account of important methodological differences between studies which may have created biased estimates. The aim of this review is to estimate the prevalence of PsA within the adult general population worldwide, considering potential differences between population-based and health administrative studies separately. METHODS: Four electronic databases were systematically searched for articles reporting the prevalence of PsA. Data were pooled to generate worldwide prevalence estimates. Where sufficient data were available, results were summarised by continent. RESULTS: 30 studies were identified, with half from Europe (n = 15). Thirteen population-based studies were identified comprising >92 000 adults, plus 17 studies (>180 million adults) based on health administrative data. The worldwide prevalence of PsA was 112 per 100 000 adults. The prevalence of PsA estimated using populations-based studies was 113 per 100 000 with continent-specific estimates of 207 (Europe), 64 (North America), and 37 (Asia) per 100 000. Health administrative studies gave a global prevalence of 109 per 100 000 with continent-specific prevalence of 175 (Europe), 147 (North America), 78 (Asia), and 17 (South America). CONCLUSION: This review compiles currently available estimates of PsA prevalence in the general population into global and continent-based estimates and considers important study design characteristics. There is wide variability between continents and data in some geographical areas are sparse but available evidence suggests that PsA is more common in Europe and North America compared with Asia and South America, and current best estimates suggest a global prevalence of 112 per 100 000 adults.

Effectiveness of remotely delivered motivational conversations on health outcomes in patients living with musculoskeletal conditions: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of remotely delivered motivational conversations on health outcomes in musculoskeletal populations. METHODS: Four electronic databases (inception-March 2022) were searched and combined with grey literature. Randomised control trials (RCTs) evaluating the effect of remotely delivered motivational conversation-based interventions within musculoskeletal populations, using valid measures of pain, disability, quality of life (QoL), or self-efficacy were included. Overall quality was assessed using GRADE criteria. Meta-analyses were performed using random effects models with pooled effect sizes expressed as standardised mean differences ( ± 95%CIs). RESULTS: Twelve RCTs were included. Meta-analyses revealed very-low to moderate quality evidence that remote interventions have a positive effect on pain and disability both immediately post intervention and at long-term follow-up compared to control, and have a positive effect on self-efficacy immediately post intervention. There was no effect on QoL immediately post intervention or at long-term follow up. CONCLUSION: Remotely delivered motivation-based conversational interventions have a positive effect on pain, disability, and self-efficacy but not on QoL. PRACTICE IMPLICATIONS: Motivational conversations, delivered remotely, may be effective in improving some health-related outcomes in MSK populations. However, higher quality evidence is needed to determine optimal intervention durations, and dosing frequencies using sufficient sample sizes and follow-up time frames.

Supporting physical activity through co-production in people with severe mental ill health (SPACES): protocol for a randomised controlled feasibility trial.

BACKGROUND: Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. METHOD: This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. DISCUSSION: This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. TRIAL REGISTRATION: ISRCTN: ISRCTN83877229. Registered on 09.09.2022.

Climate is changing, are European bats too? A multispecies analysis of trends in body size.

Animal size, a trait sensitive to spatial and temporal variables, is a key element in ecological and evolutionary dynamics. In the context of climate change, there is evidence that some bat species are increasing their body size via phenotypic responses to higher temperatures at maternity roosts. To test the generality of this response, we conducted a >20-year study examining body size changes in 15 bat species in Italy, analysing data from 4393 individual bats captured since 1995. In addition to examining the temporal effect, we considered the potential influence of sexual dimorphism and, where relevant, included latitude and altitude as potential drivers of body size change. Contrary to initial predictions of a widespread increase in size, our findings challenge this assumption, revealing a nuanced interplay of factors contributing to the complexity of bat body size dynamics. Specifically, only three species (Myotis daubentonii, Nyctalus leisleri, and Pipistrellus pygmaeus) out of the 15 exhibited a discernible increase in body size over the studied period, prompting a reassessment of bats as reliable indicators of climate change based on alterations in body size. Our investigation into influencing factors highlighted the significance of temperature-related variables, with latitude and altitude emerging as crucial drivers. In some cases, this mirrored patterns consistent with Bergmann's rule, revealing larger bats recorded at progressively higher latitudes (Plecotus auritus, Myotis mystacinus, and Miniopterus schreibersii) or altitudes (Pipistrellus kuhlii). We also observed a clear sexual dimorphism effect in most species, with females consistently larger than males. The observed increase in size over time in three species suggests the occurrence of phenotypic plasticity, raising questions about potential long-term selective pressures on larger individuals. The unresolved question of whether temperature-related changes in body size reflect microevolutionary processes or phenotypic plastic responses adds further complexity to our understanding of body size patterns in bats over time and space.

Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice.

OBJECTIVES: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. PATIENTS AND METHODS: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. RESULTS: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02]). CONCLUSION: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.

A small and vigorous black hole in the early Universe.

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang1-3. Models consider different seeding and accretion scenarios4-7, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.6, revealing the detection of the [NeIV]λ2423 and CII*λ1335 transitions (typical of active galactic nuclei), as well as semi-forbidden nebular lines tracing gas densities higher than 109 cm-3, typical of the broad line region of active galactic nuclei. These spectral features indicate that GN-z11 hosts an accreting black hole. The spectrum also reveals a deep and blueshifted CIVλ1549 absorption trough, tracing an outflow with velocity 800-1,000 km s-1, probably driven by the active galactic nucleus. Assuming local virial relations, we derive a black hole mass of log ( M BH / M ⊙ ) = 6.2 ± 0.3 , accreting at about five times the Eddington rate. These properties are consistent with both heavy seeds scenarios and scenarios considering intermediate and light seeds experiencing episodic super-Eddington phases. Our finding explains the high luminosity of GN-z11 and can also provide an explanation for its exceptionally high nitrogen abundance.

Higher and bigger: How riparian bats react to climate change.

The altitudinal distribution of animals and changes in their body size are effective indicators of climate change. Bats are sensitive to climate change due to their dependence on temperature during critical life stages. However, long-term studies documenting responses over extended periods are rare. We present a 24-year investigation of Myotis daubentonii, a riparian bat known for altitudinal sexual segregation, along a river course in Central Italy. While males occupy the entire river course, females are confined to downstream warmer areas supporting successful reproduction due to improved foraging site productivity. In 2000, females were absent above 900 m a.s.l in our study area. We hypothesise that a) this altitude threshold is now higher, due to thermal gradient changes along the river course; and b) thermoregulatory costs for reproductive females have declined, leading to increased energy investment in offspring and subsequent generational growth in bat body size. Confirming our hypotheses, females exhibited a 175-m upward shift in altitude limit. Furthermore, we found a concurrent increase in body size (but not condition). Temperatures increased in the 24 years, likely allowing females to extend their range to higher elevations and favouring an increase in newborn body mass. Riparian vegetation remained unchanged, excluding habitat quality changes as the cause for the observed responses. The rapid female elevation rise might imply future disruption of established social structures, altering intra- and intersexual competition for roosts and food. Given the global decline in insect populations, larger bats might face future difficulties in finding food to sustain their body size, increasing mortality. However, the full impact of such changes on bat fitness remains unexplored and warrants further investigation, including other bat populations. This knowledge is crucial for informing conservation in the face of ongoing climate change and preserving the ecosystem services bats deliver in riparian ecosystems.

Temporal dynamics of the early immune response following Mycobacterium bovis infection of cattle.

Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.

Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.