Diagnosis and management of placentitis with severe funisitis in a multiparous Warmblood mare.

Placentitis is an important cause of reproductive losses in the equine industry. Many cases of clinical placentitis are not diagnosed until late in the course of the disease, and for this reason there is variability in the timing of intervention, diagnostic measurements, and treatment protocols. An 8-year-old multiparous Dutch Warmblood mare that was recently exposed to EHV-1 in the herd of origin presented for routine foaling management. Placentitis was diagnosed upon intake, and medical treatment was initiated. The mare delivered a term foal, and diagnostics for infectious etiology were unrewarding. While there were obvious clinical signs supporting a diagnosis of placentitis, histopathologic examination did not reveal active inflammatory lesions in the chorioallantois; however, severe funisitis was present. This report reviews early diagnosis and management of placentitis, demonstrates an array of classic and subtle pathologic lesions seen on microscopic examination, and discusses pathophysiology of placentitis.

Determination of optimal experimental conditions for accurate 3D reconstruction of the magnetization vector via XMCD-PEEM.

This work presents a detailed analysis of the performance of X-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM) as a tool for vector reconstruction of magnetization. For this, 360° domain wall ring structures which form in a synthetic antiferromagnet are chosen as the model to conduct the quantitative analysis. An assessment is made of how the quality of the results is affected depending on the number of projections that are involved in the reconstruction process, as well as their angular distribution. For this a self-consistent error metric is developed which allows an estimation of the optimum azimuthal rotation angular range and number of projections. This work thus proposes XMCD-PEEM as a powerful tool for vector imaging of complex 3D magnetic structures.

The role of platelet-rich plasma in androgenetic alopecia: A systematic review.

BACKGROUND: Androgenetic alopecia (AGA), also referred to as male or female pattern hair loss, is the commonest cause of chronic hair loss and affects up to 80% of men by the age of 70. Despite a high prevalence, there are few approved therapies, which show minimal efficacy. OBJECTIVES: This systematic review aims to evaluate the efficacy of platelet-rich plasma (PrP) in the treatment of AGA in male patients. METHODS: MEDLINE, EMBASE, Cochrane (CENTRAL), CINAHL, clinicaltrials.gov, Google Scholar and the Science Citation Index database were searched to identify eligible studies. All randomized controlled trials (RCTs) and prospective cohort studies related to PrP use in AGA were included. Primary outcomes included changes in hair density and hair count. Methodological quality was assessed using bias assessment tools. RESULTS: Eight RCTs and one cohort study were included in the review with a total of 291 participants. Six studies reported a statistically significant increase in hair density in the PrP group versus the control. Five studies reported a statistically significant increase in hair count with PrP. Seven studies showed moderate risk and two showed low risk of bias. CONCLUSION: In a methodologically robust review on the effectiveness of PrP on male AGA, PrP demonstrated some potential to be used therapeutically. However, the low quality of evidence, moderate risk of bias, and high heterogeneity of included studies limit inferences and call for more robust designs to investigate this further.

Controlled evolution of three-dimensional magnetic states in strongly coupled cylindrical nanowire pairs.

Cylindrical magnetic nanowires are promising systems for the development of three-dimensional spintronic devices. Here, we simulate the evolution of magnetic states during fabrication of strongly-coupled cylindrical nanowires with varying degrees of overlap. By varying the separation between wires, the relative strength of exchange and magnetostatic coupling can be tuned. Hence, we observe the formation of six fundamental states as a function of both inter-wire separation and wire height. In particular, two complex three-dimensional magnetic states, a 3D Landau Pattern and a Helical domain wall, are observed to emerge for intermediate overlap. These two emergent states show complex spin configurations, including a modulated domain wall with both Néel and Bloch character. The competition of magnetic interactions and the parallel growth scheme we follow (growing both wires at the same time) favours the formation of these anti-parallel metastable states. This works shows how the engineering of strongly coupled 3D nanostructures with competing interactions can be used to create complex spin textures.

Social Network Factors Affect Nutrition Risk in Middle-Aged and Older Adults: Results from the Canadian Longitudinal Study on Aging.

OBJECTIVES: To determine which social network, demographic, and health-indicator variables are associated with SCREEN-8 (nutrition risk) scores at two time points, three years apart, using data from the Canadian Longitudinal Study on Aging. DESIGN: A retrospective cross-sectional study. SETTING AND PARTICIPANTS: 17051 Canadians aged 45 years and older with data from baseline and first follow-up of the Canadian Longitudinal Study on Aging. MEASUREMENTS: Nutrition risk was measured using SCREEN-8. Social network factors included social network size, frequency of contact with social network members, social participation, social support, self-rated social standing, and household income. Demographic variables included age, sex assigned at birth, marital status, educational attainment, and living situation (alone or with others). Health-indicator variables included depression, disability, and self-rated general health, mental health, healthy aging, and oral health. Multivariable linear regression was used to analyze the relationship between the social network, demographic, and health-indicator variables and SCREEN-8 scores at two time points, three years apart. RESULTS: Among the social network variables, individuals with higher social participation, self-rated social standing, and social support had higher SCREEN-8 scores at baseline and follow-up. Among the demographic variables, individuals who were single or widowed, compared to married or partnered, had lower SCREEN-8 scores at both time points. For the health-indicator variables, individuals who screened negative for depression, and those with higher self-rated general health, healthy aging, and oral health had higher SCREEN-8 scores at both time points. At baseline, as age increased, SCREEN-8 scores also increased. CONCLUSION: Individuals with low social participation, low social standing, and low social support may be at increased nutrition risk and should be proactively screened by healthcare professionals. Interventions and community programs designed to increase levels of social participation and foster social support may help to reduce the prevalence of nutrition risk.

Development of a convolutional neural network (CNN) based assessment exercise recommendation system for individuals with chronic stroke: a feasibility study.

BACKGROUND: The use of artificial intelligence (AI) is revolutionizing nearly every aspect of healthcare, but the application of AI in rehabilitation is lagging behind. Clinically, gait parameters and patterns are used to evaluate stroke-specific impairment. We hypothesized that gait kinematics of individuals with stroke provide rich information for the deep-learning to predict the clinical decisions made by physiotherapist. OBJECTIVE: To investigate whether the results of clinical assessments and exercise recommendations by physiotherapists can be accurately predicted using a deep-learning algorithm with gait kinematics data. METHOD: In this cross-sectional study, 40 individuals with stroke were assessed by a physiotherapist using the lower-extremity subscale of the Fugl-Meyer Assessment (FMA-LE) and Berg Balance Scale (BBS). The physiotherapist also decided whether or not the single-leg-stance was an appropriate balance training for each participant. The participants were classified as having good mobility and a low fall risk based on the cutoff scores of the two clinical scales. A convolutional neural network (CNN) was trained using gait kinematics to predict the assessment results and exercise recommendations. RESULTS: The trained model accurately predicted the results of the clinical assessments and decisions with an average prediction accuracy of 0.84 for the FMA-LE, 0.66 for the BBS, and 0.78 for the recommendation of the single-leg-stance exercise. CONCLUSIONS: This CNN deep-learning model provided time-effective and accurate prediction of clinical assessment results and exercise recommendations. This study provides preliminary evidence to support the use of biomechanical data and AI to assist treatment planning and shorten the decision-making process in rehabilitation.

Incidence, Mechanisms, and Characteristics of Injuries in Pole Dancers: A Prospective Cohort Study.

OBJECTIVE: Pole dancing is a challenging physical activity. Prospective injury studies in pole dancing are lacking. The aim of this study was to describe the incidence, mechanisms, and characteristics of injuries in pole dancers. METHODS: A total of 66 pole dancers from 41 studios across Australia were prospectively followed over 12 months. An intake questionnaire was administered including items on pole dancers' demographics and training characteristics. Exposure was assessed using a daily online training diary. Self-reported injury data were collected via an incident report form and subsequently coded using the Orchard Sports Injury Classification System. Injuries occurring during pole-specific and pole-related activities were included in the analyses. RESULTS: The sample included 63 females and 3 males, mean age 32.3 ± 8.9 years and mean pole training experience 3.5 ± 2.8 years. 25 of 66 participants completed the full study. The 1-year incidence of all new injuries was 8.95/1,000 exposure hours (95% CI 6.94 - 10.96), 7.65/1,000 hrs (95% CI 5.79 - 9.51) for pole-specific injuries and 1.29/1,000 hrs (95% CI 0.53 - 2.06) for pole-related injuries. A total of 103 injuries occurred, 62.1% of which were sudden onset and 37.9% gradual onset. Mechanism of onset included 54.4% acute and 45.6% repetitive in nature. Shoulder (20.4%) and thigh (11.7%, majority ham¬string) were the most reported anatomic injury sites. Non-contact mechanisms accounted for the majority of injuries (57.3%). The most reported primary contributor to injury onset at the shoulder were manoeuvres characterised by loaded internal humeral rotation (33.3%), and at the hamstring were manoeuvres and postures involving front splits (100.0%). CONCLUSION: The findings indicate that pole dancers are at high risk for injuries. Future research is needed to understand the biomechani¬cal demand of manoeuvres and training characteristics of pole dancing (e.g., workload and recovery) to guide the development of preventative interventions, particularly targeted toward the shoulder and hamstring.

Immediate effects of transcutaneous electrical nerve stimulation on gait patterns in chronic stroke survivors: A single group, pretest-posttest clinical trial.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has been used to reduce muscle spasticity and improve locomotion in stroke survivors. We speculate that acute changes in gait performance after TENS mediate functional improvement in the long-term. However, no previous study has investigated the effect of TENS on ankle kinetics and kinematics during walking in stroke survivors. PURPOSE: We aimed to investigate whether TENS applied over the paretic leg could rapidly improve the plantar flexion moment and ankle kinematics in chronic stroke survivors with lower limb paresis. METHODS: Twenty chronic stroke survivors were recruited. They underwent 30 min of TENS over the area innervated by the common peroneal nerve on the paretic leg. Three-dimensional (3D) motion capture was performed and ankle plantar flexor spasticity was assessed before and immediately after stimulation. Ankle kinematics and kinetic and spatiotemporal data were collected using 3D motion capture. Ankle plantar flexor spasticity was assessed using the Modified Tardieu Scale. PRINCIPAL RESULTS: A significant increase in the ankle plantar flexion moment of the paretic side during the pre-swing phase was observed immediately after stimulation (p = 0.009, maximal mean difference = 0.035, 95%CI = 0.0125 to 0.0575). The step length of the paretic limb also increased significantly after stimulation (p = 0.023, mean difference = -0.02, 95%CI = -0.04 to -0.004). TENS had no immediate effect on paretic ankle spasticity, as measured by the Modified Tardieu Scale, or on other temporo-spatial parameters. CONCLUSION: The findings support the use of TENS to improve the motor function and gait pattern in chronic stroke survivors. The study indicated that the application of TENS to the paretic leg before gait training might improve rehabilitation outcomes. Future studies investigating the effects of TENS on functional outcomes, the optimal stimulation duration, and assessing spasticity using more sensitive measures are warranted.

Structural characterization of human importin alpha 7 in its cargo-free form at 2.5 Å resolution.

Shuttling of macromolecules between nucleus and cytoplasm is a tightly regulated process mediated through specific interactions between cargo and nuclear transport proteins. In the classical nuclear import pathway, importin alpha recognizes cargo exhibiting a nuclear localization signal, and this complex is transported through the nuclear pore complex by importin beta. Humans possess seven importin alpha isoforms that can be grouped into three subfamilies, with many cargoes displaying specificity towards these importin alpha isoforms. The cargo binding sites within importin alpha isoforms are highly conserved in sequence, suggesting that specificity potentially relies on structural differences. Structures of some importin alpha isoforms, both in cargo-bound and free states, have been previously solved. However, there are currently no known structures of cargo free importin alpha isoforms within subfamily 3 (importin alpha 5, 6, 7). Here, we present the first crystal structure of human importin alpha 7 lacking the IBB domain solved at 2.5 Å resolution. The structure reveals a typical importin alpha architecture comprised of ten armadillo repeats and is most structurally conserved with importin alpha 5. Very little difference in structure was observed between the cargo-bound and free states, implying that importin alpha 7 does not undergo conformational change when binding cargo. These structural insights provide a strong platform for further evaluation of structure-function relationships and understanding how isoform specificity within the importin alpha family plays a role in nuclear transport in health and disease.

The feasibility of home monitoring of young people with cystic fibrosis: Results from CLIMB-CF.

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.

Safety and efficacy of subcutaneous alpha-tocopherol in healthy adult horses.

Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.

Synaptic weighting in single flux quantum neuromorphic computing.

Josephson junctions act as a natural spiking neuron-like device for neuromorphic computing. By leveraging the advances recently demonstrated in digital single flux quantum (SFQ) circuits and using recently demonstrated magnetic Josephson junction (MJJ) synaptic circuits, there is potential to make rapid progress in SFQ-based neuromorphic computing. Here we demonstrate the basic functionality of a synaptic circuit design that takes advantage of the adjustable critical current demonstrated in MJJs and implement a synaptic weighting element. The devices were fabricated with a restively shunted Nb/AlOx-Al/Nb process that did not include MJJs. Instead, the MJJ functionality was tested by making multiple circuits and varying the critical current, but not the external shunt resistance, of the oxide Josephson junction that represents the MJJ. Experimental measurements and simulations of the fabricated circuits are in good agreement.

Imaging three-dimensional magnetic systems with x-rays.

Recent progress in nanofabrication and additive manufacturing have facilitated the building of nanometer-scale three-dimensional (3D) structures, that promise to lead to an emergence of new functionalities within a number of fields, compared to state-of-the-art two dimensional systems. In magnetism, the move to 3D systems offers the possibility for novel magnetic properties not available in planar systems, as well as enhanced performance, both of which are key for the development of new technological applications. In this review paper we will focus our attention on 3D magnetic systems and how their magnetic configuration can be retrieved using x-ray magnetic nanotomography. We will start with an introduction to magnetic materials, and their relevance to our everyday life, along with the growing impact that they will have in the coming years in, for example, reducing energy consumption. We will then briefly introduce common methods used to study magnetic materials, such as electron holography, neutron and x-ray imaging. In particular, we will focus on x-ray magnetic circular dichroism (XMCD) and how it can be used to image magnetic moment configurations. As a next step we will introduce tomography for 3D imaging, and how it can be adapted to study magnetic materials. Particular attention will be given to explaining the reconstruction algorithms that can be used to retrieve the magnetic moment configuration from the experimental data, as these represent one of the main challenges so far, as well as the different experimental geometries that are available. Recent experimental results will be used as specific examples to guide the reader through each step in order to make sure that the paper will be accessible for those interested in the topic that do not have a specialized background on magnetic imaging. Finally, we will describe the future prospects of such studies, identifying the current challenges facing the field, and how these can be tackled. In particular we will highlight the exciting possibilities offered by the next generation of synchrotron sources which will deliver diffraction limited beams, as well as with the extension of well-established methodologies currently implemented for the study of two-dimensional magnetic materials to achieve higher dimensional investigations.

Head and Neck Cancer Immunotherapy beyond the Checkpoint Blockade.

The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients with HNSCC respond to immune checkpoint inhibitors, underscoring the critical need to alleviate cancer resistance to immunotherapy. Major advances have been made to elucidate the intrinsic and adaptive resistance mechanisms to immunotherapy. Central genomic events in HNSCC have been found to possess previously unknown roles in suppressing immune sensing. Such inhibitory function affects both the innate and adaptive arms of tumor-specific immunity. While checkpoint blockade effectively reinvigorates adaptive T-cell responses, additional targeting of the oncogenic inhibitors of innate immune sensing likely informs a novel and potent strategy for immune priming. This review discusses the recent advances on the identification of key HNSCC oncogenes that impair antitumor immunity and emerging immune-priming approaches that sensitize poorly immunogenic HNSCCs to checkpoint blockade. These approaches include but are not limited to cancer vaccine systems utilizing novel type I interferon agonists as immune adjuvants, radiation, DNA damage-inducing agents, and metabolic reprogramming. The goal of these multipronged approaches is to expand tumor-specific effector T-cells, break checkpoint receptor-mediated tolerance, and metabolically support sustained T-cell activation. The translation of therapeutics that reverses oncogenic inhibition of immune sensing requires thorough characterization of the HNSCC regulators of innate immune sensors, development of additional immunocompetent HNSCC mouse models, as well as engineering of more robust immune adjuvant delivery systems. Built on the success of checkpoint blockade, validation of novel immune-priming approaches holds key promises to expand the pool of responders to immunotherapy.

Ret Signaling Is Required for Tooth Pulp Innervation during Organogenesis.

During organogenesis, the timing and patterning of dental pulp innervation require both chemoattractive and chemorepellent cues for precise spatiotemporal regulation. Our understanding of the signaling mechanisms that regulate tooth innervation during development, as well as the basic biology of these sensory neurons, remains rudimentary. In this study, we analyzed the expression and function of glial cell line-derived neurotrophic factor (GDNF) and its receptor tyrosine kinase, Ret, in the regulation of innervation of the mouse tooth pulp by dental pulpal afferent (DPA) neurons of the trigeminal ganglion (TG). Using reporter mouse models, we demonstrate that Ret is highly expressed by a subpopulation of DPA neurons projecting to the tooth pulp at both postnatal day 7 (P7) and in the adult. In the adult tooth, GDNF is highly expressed by many cell types throughout the dental pulp. Using a ubiquitous tamoxifen (TMX)-inducible Cre ( UBC-Cre/ERT2) line crossed to Ret conditional knockout mice ( Retfx/fx), Ret was deleted immediately prior to tooth innervation, and the neural projections into P7 molars were analyzed. TMX treatment was efficient in ablating >95% of Ret protein. We observed that UBC-Cre/ERT2; Retfx/fx mice had a significant reduction in the total number of neurites present within the pulp at P7, with a significant accumulation of aberrant fibers in the dental follicle and periodontium. In agreement with these findings, inhibition of Ret signaling through in vivo administration of a highly specific pharmacologic inhibitor (1NM-PP1) of Ret also caused a substantial reduction in pulpal innervation. Taken together, these findings indicate that Ret signaling regulates the timing and patterning of tooth innervation by dental primary afferent neurons of the TG during organogenesis and provide a rationale to explore whether alterations in the GDNF-Ret pathway contribute to pathophysiological conditions in the adult dentition.

Children with cerebral palsy have larger Achilles tendon moment arms than typically developing children.

The effectiveness of the plantarflexor muscle group to generate desired plantarflexion moments is modulated by the geometry of the Achilles tendon moment arm (ATMA). Children with cerebral palsy (CP) frequently have reduced plantarflexion function, which is commonly attributed to impaired muscle structure and function, however little attention has been paid to the potential contribution of ATMA geometry. The use of musculoskeletal modelling for the simulation of gait and understanding of gait mechanics, rely on accuracy of ATMA estimates. This study aimed to compare 3D in-vivo estimates of ATMA of adults, children with CP and typically developing (TD) children, as well as compare 3D in-vivo estimates to linearly scaled musculoskeletal model estimates. MRI scans for eight children with CP, 11 TD children and nine healthy adults were used to estimate in-vivo 3D ATMA using a validated method. A lower limb musculoskeletal model was linearly scaled to individual tibia length to provide a scaled ATMA estimate. Normalised in-vivo 3D ATMA for children with CP was 17.2% ±â€¯2.0 tibia length, which was significantly larger than for TD children (15.2% ±â€¯1.2, p = 0.013) and adults (12.5% ±â€¯0.8, p < 0.001). Scaled ATMA estimates from musculoskeletal models significantly underestimated in-vivo estimates for all groups, by up to 34.7%. The results of this study show children with CP have larger normalised 3D ATMA compared to their TD counterparts, which may have implications in understanding reduced plantarflexor function and the efficacy of surgical interventions whose aim is to modify the musculoskeletal geometry of this muscle group.

Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck.

INTRODUCTION: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed. METHODS: Immunohistologic expression of markers was determined in tissue microarrays from 274 previously untreated HNSCC patients. Expression was correlated with levels of TILs in microcores and WPOI in biopsy specimens. Correlations were assessed by Kruskal-Wallis testing and Spearman correlation coefficients where appropriate. Overall and relapse-free survival were analyzed with Cox proportional hazards models. Median follow up was 60.0 months. RESULTS: Loss of E-cadherin expression was significantly associated with low or absent SOX2 expression (R = 0.433, p < 0.0001). SOX2 expression and low grade WPOI were significantly associated with favorable overall (OS) and relapse free (RFS) survival in multivariable analysis. E-cadherin expression did not correlate with TILs, however WPOI score correlated indirectly with CD4, CD8, and FoxP3 levels. When grouped by primary treatment, lower grades (1, 2) of WPOI predicted improved RFS and OS in patients treated with primary surgery but not for patients treated with chemoradiation. CONCLUSION: The findings suggest that SOX2 expression and WPOI are significant prognostic factors and that WPOI correlates with decreased T cell infiltration. The combination of markers and TILs might be useful in selecting patients for primary surgery.

Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning.

CYD-TDV is the first licensed dengue vaccine for individuals 9-45 (or 60) years of age. Using 12% of the subjects enroled in phase-2b and phase-3 trials for which baseline serostatus was measured, the vaccine-induced protection against virologically confirmed dengue during active surveillance (0-25 months) was found to vary with prior exposure to dengue. Because age and dengue exposure are highly correlated in endemic settings, refined insight into how efficacy varies by serostatus and age is essential to understand the increased risk of hospitalisation observed among vaccinated individuals during the long-term follow-up and to develop safe and effective vaccination strategies. Here we apply machine learning to impute the baseline serostatus for subjects with post-dose 3 titres but missing baseline serostatus. We find evidence for age dependence in efficacy independent of serostatus and estimate that among 9-16 year olds, CYD-TDV is protective against serotypes 1, 3 and 4 regardless of baseline serostatus.

Fatigue and depression predict reduced health-related quality of life in childhood-onset lupus.

We aimed to identify risk factors for persistently reduced health-related quality of life in childhood-onset lupus and describe a risk profile for persistently reduced health-related quality of life. At a tertiary rheumatology clinic, 50 childhood onset lupus patients were assessed twice, approximately six months apart. Measures of disease activity and patient-reported measures of health-related quality of life, pain, depressive symptoms, anxiety and disability were collected at each visit. At visits 1 and 2, respectively, clinically relevant fatigue was present in 66% and 56% of patients; clinically significant depressive symptoms in 26% and 24%; and clinically significant anxiety in 34% and 28%. Poorer health-related quality of life at follow-up was significantly predicted by higher fatigue and depressive symptoms at the initial visit. Using clinically relevant cut-offs for fatigue and depressive symptoms, patients were assigned to Low ( n = 27) or High Risk ( n = 23) groups. A profile of significantly greater pain, anxiety and coping difficulties was seen in the High Risk group. Routine assessment of fatigue and mood symptoms in youth with childhood-onset lupus could be helpful in identifying those at risk for persistently poor health-related quality of life. Integration of behavioral interventions to address fatigue and mood symptoms into medical care for such patients may be beneficial, but more research in this area is needed.