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Introduction: High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations. Methods: Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models. Results: Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200 mg + MTX/csDMARD exhibited consistently better responses after 12 weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population. Conclusion: The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA. Trial Registration: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728. Plain Language Summary: Rheumatoid arthritis is a disease that results in swollen and painful joints. There is currently no method to determine which treatment will work best for an individual patient. However, there may be identifying markers found in the blood that could indicate how a patient will respond to treatment. One of these possible markers is a ratio of two types of white blood cells, neutrophils and lymphocytes, which are part of the body's immune system and help the body detect and fight infection and other diseases. This ratio is referred to as the neutrophil-to-lymphocyte ratio. The current study evaluated whether the neutrophil-to-lymphocyte ratio at the beginning of treatment was associated with rheumatoid arthritis treatment outcomes. Blood test results were used from 3365 patients receiving filgotinib (a medicine used to treat rheumatoid arthritis) or other therapies as part of the FINCH clinical trials. Patients were classified as having a high or low neutrophil-to-lymphocyte ratio at the start of treatment. Patients receiving filgotinib over 24 weeks who had a high neutrophil-to-lymphocyte ratio showed less disease activity than patients whose ratio was low. This study provides support for the use of the neutrophil-to-lymphocyte ratio as a way to help determine whether a patient would benefit from filgotinib as part of their rheumatoid arthritis treatment and may help improve rheumatoid arthritis treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Self-harm is a prevalent behaviour that has a major detrimental impact on a person's life. Psychological therapies have the potential to help, but evidence of effective interventions remains limited. Access and acceptability of interventions can also be a significant challenge, with individuals either being unable to access help or having to endure long waiting lists. Cognitive analytic therapy (CAT) is a time-limited and relationally-focused psychotherapy that may provide a valuable treatment option for people who self-harm. This protocol outlines the methodology for the first feasibility randomised controlled trial (RCT) of CAT for adults that self-harm. The trial will aim to determine the feasibility, acceptability and safety of undertaking larger-scale evaluations of CAT for self-harm within an RCT context. Method: An RCT design with 1:1 allocation to CAT plus treatment as usual (TAU) or TAU alone. Participants will be adult outpatients with three or more instances of self-harm in the past year (target sample of n = 60). CAT will be 8 one-to-one weekly 60-min sessions plus a follow-up session up to 8 weeks after the last session. Assessments will occur at baseline, 12 weeks and 18 weeks after randomisation. Qualitative interviews with participants will gain insights into the feasibility and acceptability of CAT. Feasibility outcomes will be judged against progression criteria. Discussion: CAT may be an effective and accessible treatment option for people who self-harm, providing a more relationally orientated alternative to more behavioural therapies. The proposed feasibility RCT is an important first step in evaluating CAT as a treatment for self-harm. Trial registration: The trial was pre-registered (21/10/22) on ISR CTN (ISRCTN code: ISRCTN75661422). [ABSTRACT FROM AUTHOR]

A relatively simple 1D RANS model of the time evolution of the planetary boundary layer is extended to include water vapor and cloud droplets plus transfers between them. Radiative fluxes and flux divergence are also included. An underlying ocean surface is treated as a source of water vapor and as a sink for cloud or fog droplets. With a constant sea surface temperature and a steady wind, initially dry or relatively dry air will moisten, starting at the surface. Turbulent boundary layer mixing will then lead towards a layer with a well-mixed potential temperature (and so temperature decreasing with height) and well-mixed water vapor mixing ratio. As a result, the air will, sooner or later, become saturated at some level, and a stratus cloud will form. [ABSTRACT FROM AUTHOR]

In the paper, with the aid of the Faà di Bruno formula, in terms of the central factorial numbers and the Stirling numbers of the second kinds, the authors derive several series expansions for any positive integer powers of the sinc and sinhc functions, discover several closed-form expressions for partial Bell polynomials of all derivatives of the sinc function, establish several series expansions for any real powers of the sinc and sinhc functions, and present several identities for central factorial numbers of the second kind and for the Stirling numbers of the second kind. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint pain and stiffness. Biologics represent some of the most effective treatments for RA, but previous guidance from the National Institute for Health and Care Excellence (NICE) has limited their use to patients with severely active disease. This has meant patients with moderately active RA have been treated as if they have an acceptable disease state, despite many cases where the inflammation has a major impact on joint damage, mobility, pain and quality of life. However, recent guideline changes (NICE TA715) have approved the use of three biologics — adalimumab, etanercept and infliximab — for the treatment of moderately active RA. Main body: In response to these changes, we have held discussions with medical teams from across the UK to consider the main implications for implementation of these new recommendations, as well as any differences in approach that may exist at a local level. Several key challenges were identified. These included establishing methods of educating both physicians and patients concerning the new availability of the biologic treatments, with suggestions of various organisations that could be approached to circulate informative material. Identifying which patients with moderately active RA stand to benefit was another discussion topic. Relying solely on scoring systems like Disease Activity Score in 28 Joints (DAS28) was acknowledged to have limitations, and alternative complementary approaches such as ultrasound, as well as assessing a patient's co-morbidities, could also be useful tools in determining those who could benefit from biologics. An additional challenge for the process of patient identification has been the increase in the use of telemedicine consultations in response to the coronavirus disease 2019 (COVID-19) pandemic. More use of patient-reported outcomes was raised as one possible solution, and the importance of maintaining up-to-date databases on patient disease scores and treatment history was also stressed. Conclusion: While challenges exist in education and identifying patients who may benefit from the use of biologics, the NICE TA715 recommendations hold great potential in addressing an unmet need for the treatment of moderate RA. [ABSTRACT FROM AUTHOR]

The influenza pandemic of 1918-19 was the most devastating pandemic of the 20th century. It killed an estimated 50–100 million people worldwide. In late 1918, when the severity of the disease was apparent, the Australian Quarantine Service was established. Vessels returning from overseas and inter-state were intercepted, and people were examined for signs of illness and quarantined. Some of these vessels carried the infection throughout their voyage and cases were prevalent by the time the ship arrived at a Quarantine Station. We study four outbreaks that took place on board the Medic, Boonah, Devon, and Manuka in late 1918. These ships had returned from overseas and some of them were carrying troops that served in the First World War. By analysing these outbreaks under a stochastic Bayesian hierarchical modeling framework, we estimate the transmission rates among crew and passengers aboard these ships. Furthermore, we ask whether the removal of infectious, convalescent, and healthy individuals after arriving at a Quarantine Station in Australia was an effective public health response. Author summary: The influenza pandemic of 1918–19 was one of the deadliest pandemics in history. In Australia, when it was apparent that the virus was severe, a quarantine service was established to intercept and quarantine ships that returned from overseas and travelled interstate. In this study, we look at the records of outbreaks on board the Medic, Boonah, Devon, and Manuka. Some of the ships carried surviving troops from the First World War, and infections were prevalent when they arrived at a quarantine station. Infectious, convalescent, and healthy individuals on board were moved to the quarantine station for treatment or isolation. We model the outbreaks on the four ships using stochastic epidemic models and estimate the model parameters within a hierarchical framework. Furthermore, we investigate whether the removal of individuals with various disease states was an effective intervention measure from a public health perspective. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to evaluate protein biomarker changes related to the administration of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) with inadequate response to methotrexate. Methods: Plasma and serum samples were collected from patients enrolled in FINCH 1 (NCT02889796), a Phase 3 trial. Patients with stable backgrounds of methotrexate were randomly assigned once-daily oral filgotinib 200 or 100 mg, subcutaneous adalimumab 40 mg every 2 weeks (W), or placebo. Up to 35 biomarkers were analyzed at baseline, W4, and W12 with enzyme-linked immunosorbent assays and chemiluminescence and electrochemiluminescence assays. Results: At baseline, four distinct biomarker clusters were identified. The strongest intragroup correlations were in bone-cartilage resorption/inflammation and JAK/signal transducer and activator of transcription (STAT) signaling activity. At baseline, significant positive correlations were identified for cytokines with patient-reported pain and with patient measures of fatigue. Filgotinib reduced levels of cytokines associated with inflammation and cell migration as early as W4 and through W12. Compared to adalimumab, filgotinib induced significant reductions in bone-related turnover biomarkers, N-telopeptide of type 1 collagen and C-telopeptide 1, as well as biomarkers associated with baseline disease activity. No baseline predictors of therapeutic response to filgotinib were identified. Conclusions: Filgotinib reduced peripheral protein biomarkers associated with JAK/STAT signaling, inflammatory signaling, immune cell migration, and bone resorption as soon as W4 in FINCH 1. Effects were dose-dependent and consistent with the clinical efficacy of filgotinib observed in FINCH 1. The changes in peripheral biomarkers associated with filgotinib treatment in methotrexate-experienced patients are consistent with changes observed in both methotrexate-naïve and biologic disease-modifying antirheumatic drug-experienced RA populations. These data demonstrate dose-dependent effects of preferential JAK1 inhibition by filgotinib on peripheral blood protein biomarkers in methotrexate-experienced patients with RA. Trial Registration: ClinicalTrials.gov, NCT02889796. [ABSTRACT FROM AUTHOR]

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active rheumatoid arthritis (RA) and provides improvements in clinical signs, symptoms and patient-reported outcomes. Currently, baricitinib is approved for treating RA in more than 75 countries. In several pivotal Phase II and III RA trials (RA-BALANCE, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BEYOND), up to seven years of baricitinib treatment was well tolerated and provided rapid and sustained efficacy, which was confirmed in real-world settings. Safety signals for another JAK inhibitor, tofacitinib, have emerged, as observed in the post-marketing Phase IIIb/IV trial Oral Rheumatoid Arthritis Trial (ORAL) Surveillance; safety signals were subsequently highlighted in a retrospective study of baricitinib and consequently new recommendations and warnings and precautions for all JAK inhibitors have been issued. Ongoing studies to further characterise and clarify the benefit:risk of JAK inhibitors include registries and controlled trials. This capstone review summarises clinical and real-world data outlining the benefit:risk profile of baricitinib, confirming that the improved disease activity and physical function of patients with RA treated with this JAK inhibitor observed in clinical trials is translated into effectiveness in clinical practice, with a low rate of discontinuations. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice. Main text: There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures. Conclusion: Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice. Main text: There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures. Conclusion: Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals. [ABSTRACT FROM AUTHOR]

Introduction: We sought to identify and compare treatment response groups based on individual patient responses (rather than group mean response) over time on the Clinical Disease Activity Index (CDAI) for rheumatoid arthritis (RA), in patients treated with baricitinib 4-mg in 4 phase 3 studies. Methods: Trajectory subgroups were identified within each study using growth mixture modeling. Following grouping, baseline characteristics and disease measures were summarized and compared. Results: In each study, three response trajectories were identified. In the three studies of patients naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) patients had, on average, high disease activity, as measured by CDAI. In these studies, a group of rapid responders (65–71% of patients) had the lowest baseline CDAI scores and achieved mean CDAI ≤ 10 by week 16. Gradual responders (10–17%) had higher baseline CDAI, but generally achieved low disease activity (CDAI ≤ 10) by week 24. A group of partial responders (18–22%) had higher baseline CDAI and did not achieve mean CDAI ≤ 10. In bDMARD-experienced patients, the subgroups were rapid responders, who achieved mean CDAI ≤ 10 (42% of patients); partial responders, with mean CDAI decrease of ~ 15 points from baseline (42% of patients); and limited responders (15% of patients). Changes in modified total sharp score (mTSS; assessed only in biologic-naïve patients) were below the smallest detectable difference at 24/52 weeks for > 90% of patients in each group, excepting partial responders in RA-BEGIN (≥ 75% no detectable change). Conclusion: In patients receiving baricitinib 4-mg, lower baseline CDAI was generally associated with rapid response, while higher baseline CDAI scores were generally seen for patients who either reached treatment targets more gradually, or who had a partial or limited response. Maintenance of response was observed with continued baricitinib treatment in all response groups and generally included maintenance of mTSS. Plain Language Summary: Baricitinib is an oral agent widely approved for the treatment of moderately to severely active rheumatoid arthritis). Although baricitinib (and other agents) have demonstrated efficacy at the population level, treatment responses vary considerably between individual patients. This study assessed four baricitinib phase 3 clinical studies and categorized patient responses into response groups based on the Clinical Disease Activity Index (CDAI) using a growth mixture model. We then evaluated baseline characteristics and corresponding disease measures within the response groups. In patients with no prior treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs), 65–71% of patients had rapid responses to treatment, while smaller groups had gradual (10–17%) or partial (18–22%) responses. In patients with prior bDMARD experience, rapid and partial responders each comprised 42% of patients while 15% had limited response. Gradual responders generally had higher baseline CDAI versus rapid responders, but achieved low disease activity (LDA) by 24, versus 12 weeks for rapid responders. Across response groups, patients who continued treatment generally maintained their response up to 52 weeks, and where joint erosion was assessed (in bDMARD-naïve patients), generally saw maintenance of joints during continued therapy. The identification of a gradual responder group, which demonstrated good response but required more time to achieve LDA, is relatively novel and should be considered when setting treatment expectations, particularly in patients with high baseline disease activity. In addition, in bDMARD-experienced patients, many patients did not achieve LDA but maintained a substantial partial response with continued therapy. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work is to compare real-world outcomes of patients with rheumatoid arthritis (RA) receiving adalimumab (ADA) bio-originator (non-switchers) to those who had switched from ADA bio-originator to an ADA biosimilar (switchers) on the basis of the hypothesis that these outcomes would differ. Methods: Data were drawn from the Adelphi RA Disease Specific Programme™, a point-in-time survey of physicians and their patients in Europe (France, Germany, Italy, Spain, UK) in 2020. Physicians completed a questionnaire for their next ten adult patients with RA, followed by four additional patients who had switched from ADA bio-originator to an ADA biosimilar (switchers). Physician- and patient-reported outcomes (PROs) for switchers and non-switchers were compared by propensity score matching. Results: Three hundred and three rheumatologists provided data for 160 non-switchers and 225 switchers, 140 patients provided data; 51 non-switchers, 89 switchers. According to physician-reported disease activity, non-switchers were more likely to improve on their current ADA treatment than switchers (68%, n = 108 vs. 26%, n = 59 p < 0.001) and less likely to worsen (1%, n = 2 vs. 9%, n = 20; p < 0.01). Physician-reported patient adherence was significantly lower amongst switchers versus non-switchers (0.66 vs. 0.78, respectively; p = 0.04). More non-switchers than switchers were reported by their physicians to be consistent in taking their RA medicine (p < 0.001). Compared with non-switchers, PRO measures indicated quality of life was worse (EQ-5D Visual Analogue Scale: 62.9 vs. 71.9; p < 0.001) and activity impairment was greater (Work Productivity Activity Index: 31.0 vs. 24.4; p = 0.02) for switchers, with trends for poorer health status and greater pain. Conclusions: Non-medical switching in RA treatment may lead to unforeseen outcomes that should be considered by health decision-makers. [ABSTRACT FROM AUTHOR]

Background: Going to university is an important milestone in many people's lives. It can also be a time of significant challenge and stress. There are growing concerns about mental health amongst student populations including suicide risk. Student mental health and counselling services have the potential to prevent suicide, but evidence-based therapies are required that fit these service contexts. The Broad-Minded Affective Coping intervention (BMAC) is a brief (6 sessions), positive imagery-based intervention that aims to enhance students access to past positive experiences and associated emotions and cognitions. Pilot data provides preliminary support for the BMAC for students struggling with suicidal thoughts and behaviours, but this intervention has not yet been evaluated in the context of a randomised controlled trial (RCT). The Mental Imagery for Suicidality in Students Trial (MISST) is a feasibility RCT that aims to determine the acceptability and feasibility of evaluating the BMAC as an intervention for university students at risk of suicide within a larger efficacy trial. Key feasibility uncertainties have been identified relating to recruitment, retention, and missing data. Intervention acceptability and safety will also be evaluated. Method: MISST is a feasibility randomised controlled trial design, with 1:1 allocation to risk assessment and signposting plus BMAC or risk assessment and signposting alone. Participants will be university students who self-report experiences of suicidal ideation or behaviour in the past 3 months. Assessments take place at baseline, 8, 16, and 24 weeks. The target sample size is 66 participants. A subset of up to 20 participants will be invited to take part in semi-structured qualitative interviews to obtain further data concerning the acceptability of the intervention. Discussion: The BMAC intervention may provide an effective, brief talking therapy to help university students struggling with suicidal thoughts that could be readily implemented into university student counselling services. Depending on the results of MISST, the next step would be to undertake a larger-scale efficacy trial. Trial registration: The trial was preregistered (17 December 2021) on ISRCTN (ISRCTN13621293) and ClinicalTrials.gov (NCT05296538). [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint pain and stiffness. Biologics represent some of the most effective treatments for RA, but previous guidance from the National Institute for Health and Care Excellence (NICE) has limited their use to patients with severely active disease. This has meant patients with moderately active RA have been treated as if they have an acceptable disease state, despite many cases where the inflammation has a major impact on joint damage, mobility, pain and quality of life. However, recent guideline changes (NICE TA715) have approved the use of three biologics — adalimumab, etanercept and infliximab — for the treatment of moderately active RA. Main body: In response to these changes, we have held discussions with medical teams from across the UK to consider the main implications for implementation of these new recommendations, as well as any differences in approach that may exist at a local level. Several key challenges were identified. These included establishing methods of educating both physicians and patients concerning the new availability of the biologic treatments, with suggestions of various organisations that could be approached to circulate informative material. Identifying which patients with moderately active RA stand to benefit was another discussion topic. Relying solely on scoring systems like Disease Activity Score in 28 Joints (DAS28) was acknowledged to have limitations, and alternative complementary approaches such as ultrasound, as well as assessing a patient's co-morbidities, could also be useful tools in determining those who could benefit from biologics. An additional challenge for the process of patient identification has been the increase in the use of telemedicine consultations in response to the coronavirus disease 2019 (COVID-19) pandemic. More use of patient-reported outcomes was raised as one possible solution, and the importance of maintaining up-to-date databases on patient disease scores and treatment history was also stressed. Conclusion: While challenges exist in education and identifying patients who may benefit from the use of biologics, the NICE TA715 recommendations hold great potential in addressing an unmet need for the treatment of moderate RA. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "Filgotinib Modulates Inflammation-Associated Peripheral Blood Protein Biomarkers in Adults with Active Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate." The correction addresses two errors in the original article. The first error is in a sentence under the "Prior Presentation" section, where the word "prevented" should have been "presented." The second error is in Table 1, where the data in the column headings for FIL200 and ADA were incorrectly aligned, and an arrow in the fifth row for IL-17A was incorrect and should have been an up arrow. The corrected table is provided in the notice. The original article has been corrected. [Extracted from the article]

This article situates, against the backdrop of the Covid-19 crisis and the many systemic inequalities the pandemic has highlighted, challenges and opportunities for researchers and commissioners of research. It provides examples from social science research of how researchers have demonstrated agility and adaptation during the pandemic in a range of contexts. It summarises findings and lessons around access and engagement, consent, ethics and incentives, and power and perspectives. It concludes that research supported by the Covid Collective is providing useful insights for doing research differently, which in turn provides real hope for research to help transform knowledge and transform lives. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy to the whole breast is standard of care following breast-conserving surgery for early breast cancer. Previously this treatment was delivered daily over 3–5 weeks. Clinical trials of shorter treatment protocols completing radiation in five treatments have been completed showing similar outcomes to longer protocols; however, there remains a lack of international consensus as to which patients are best treated with shorter regimens. Here we describe how we developed a consensus in our department for using a five-fraction regimen, using a survey of physicians and a review of the most relevant literature. Five-fraction adjuvant whole breast radiation has been shown to be a safe and effective alternative to longer fractionation regimens. Given the lack of international consensus on patient selection for the protocol, we developed a consensus protocol to guide patient selection and facilitate safe and efficient five-fraction radiation in our radiation medicine department. In developing the directive, we surveyed departmental physicians about their choice of adjuvant breast regimen for various clinical scenarios. Patient travel burden was the factor most strongly impacting radiation oncologists' decision-making when considering prescribing a five-fraction course of adjuvant breast radiation; the length of clinical trial follow-up data and acute and late normal tissue effects also impacted it, along with personal clinical experience and experience of dosimetry and physics personnel. Relative value unit (RVU) reimbursement and financial toxicity to the patient were reported to be less important in decision-making. Physicians were most comfortable using five-fraction radiation in women >50 years of age with low-risk cancer and for patients unable to attend for longer treatment courses. Eight months after implementation, the protocol accounts for 4.7% of breast irradiation delivered in our department. [ABSTRACT FROM AUTHOR]

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localizing epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 participants (21 598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We proposed that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures postoperatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions that were spared by surgery were more abnormal than those resected only in patients with persistent postoperative seizures (t = -3.6, P = 0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (area under curve 0.75 P = 0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyond. [ABSTRACT FROM AUTHOR]

Objectives The burden and treatment landscape of RA is poorly understood. This research aimed to identify evidence on quality of life, caregiver burden, economic burden, treatment patterns and clinical outcomes for patients with moderate RA in the United Kingdom. Methods A systematic literature review was performed across multiple databases and screened against pre-defined inclusion criteria. Results A total of 2610 records were screened; seven studies presenting evidence for moderate RA were included. These patients were found to incur substantial burden, with moderate to severe levels of disability. Compared with patients in remission, moderate RA patients reported higher levels of disability and decreased EQ-5D utility scores. The majority of patients did not feel that their current therapy adequately controlled their disease or provided sufficient symptom relief. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) have not approved advanced therapies (such as biological disease-modifying anti-rheumatic drugs) for patients with moderate disease, which restricts access for these patients. Conclusion The evidence available on the burden of moderate RA is limited. Despite current treatments, moderate RA still has a substantial negative impact, given that a DAS28 disease activity score defined as being in the moderate range does not qualify them for access to advanced therapies in the United Kingdom. For these patients, there is a particular need for further studies that investigate their burden and the impact of treating them earlier. Such information would help guide future treatment decisions and ensure the most effective use of resources to gain the best outcomes for patients with moderate RA. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long‐term network plasticity remain underexplored. Ten years post‐ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function.Twenty‐five ATLR patients (12 left‐sided) and 10 healthy controls underwent a memory‐encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed‐effect models probed preoperative phenotypes' effects on long‐term memory outcomes.Ten years post‐ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long‐term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL‐seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration.Our findings underscore the enduring nature of functional network reorganizations to provide long‐term cognitive support. Ten years post‐ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long‐term memory prediction and strategies for lasting memory rehabilitation. [ABSTRACT FROM AUTHOR]

The current global pandemic of Covid-19 is a health and broader crisis of overwhelming proportions, threatening livelihoods, economies, and societies, particularly those already experiencing the greatest vulnerabilities. In putting the lives of millions of people at risk, creating uncertainties, heightening existing fragilities, and exacerbating inequalities, it has become a truly global challenge. Crisis also brings opportunity, however, and in addition to short- and mid-term responses, this is a time to explore and work towards a genuine transformation of ideas, policies, programmes, and practices. This may all be encapsulated in the overall notion of 'building back a better world'. Against this backdrop, this article introduces this IDS Bulletin issue which asks, fundamentally, how we can collectively and equitably shape - and even transform - our shared future, in the light of experience of Covid-19, and what steps are necessary for us to do so. It draws upon strategic approaches guiding the efforts of two highly engaged organisations: Irish Aid, Ireland; and the Institute of Development Studies, UK. This editorial introduction explores lessons learned from the impact of Covid-19 by highlighting some key viewpoints and evidence provided in the articles3 that follow. It then offers a number of priority areas for action looking forward, as well as several principles that may help to guide those future actions in efforts to build back a better world. [ABSTRACT FROM AUTHOR]

Background: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. Objective: The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. Methods: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. Results: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥ 80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤ 1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. Conclusion: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA. [ABSTRACT FROM AUTHOR]

Reported herein is the development of assays for the spectrophotometric quantification of biocatalytic silicon−oxygen bond hydrolysis. Central to these assays are a series of chromogenic substrates that release highly absorbing phenoxy anions upon cleavage of the sessile bond. These substrates were tested with silicatein, an enzyme from a marine sponge that is known to catalyse the hydrolysis and condensation of silyl ethers. It was found that, of the substrates tested, tert-butyldimethyl(2-methyl-4-nitrophenoxy)silane provided the best assay performance, as evidenced by the highest ratio of enzyme catalysed reaction rate compared with the background (uncatalysed) reaction. These substrates were also found to be suitable for detailed enzyme kinetics measurements, as demonstrated by their use to determine the Michaelis−Menten kinetic parameters for silicatein. [ABSTRACT FROM AUTHOR]

In this paper we provide a detailed geographical analysis of the role of the New York-London (NYLON) connection in the world city network. We find that its pre-eminence is much greater and much more diverse than previously considered. Our analysis draws on a data collection of the worldwide office networks of producer services firms across cities in 2018, and applies a purposeful combination of principal components analysis and network analysis to identify the relative importance of city-dyads in different regional geographies of globalization. We review the role of NYLON in the the different city sub-nets thus identified, and provide a more focused discussion of NYLON's role in the production of three of these. In a short conclusion, we consider the meaning of our results for the broader literature. [ABSTRACT FROM AUTHOR]

The clinical spectrum of rheumatoid arthritis (RA) presentation is heterogeneous, with wide variation in age of onset, degree of joint involvement and severity. Delayed rheumatological referral is associated with less favourable long-term outcomes. Multidisciplinary teamwork is key to the success of a holistic approach to patient care and addressing issues that are important to the person. Pharmacological treatment of early RA aims to optimally suppress the inflammatory component of the disease with an ideal treatment target of remission. The overarching aim of management of early RA is to achieve a quality of life that permits the individual to pursue normal work, domestic and social activity. [ABSTRACT FROM AUTHOR]

Background: Radioiodine represents a cost-effective treatment option for Graves' disease. In the UK, it is traditionally reserved for patients who relapse after initial thionamide therapy. In a change from current practice, the new guidelines of the National Institute for Health and Care Excellence (NICE) recommends that radioiodine should now be first line therapy for Graves' disease. However, the safety of radioiodine with respect to long-term mortality risk has been the subject of recent debate. This analysis examines evidence from treatment related mortality studies in hyperthyroidism and discusses their implications for future Graves' disease treatment strategies. Main body: Some studies have suggested an excess mortality in radioiodine treated cohorts compared to the background population. In particular, a recent observational study reported a modest increase in cancer-related mortality in hyperthyroid patients exposed to radioiodine. The interpretation of these studies is however constrained by study designs that lacked thionamide control groups or information on thyroid status and so could not distinguish the effect of treatment from disease. Two studies have shown survival advantages of radioiodine over thionamide therapy, but these benefits were only seen when radioiodine was successful in controlling hyperthyroidism. Notably, increased mortality was associated with uncontrolled hyperthyroidism irrespective of therapy modality. Conclusions: Early radioiodine treatment will potentially reduce mortality and should be offered to patients with severe disease. However, thionamides are still suitable for patients with milder disease, contraindications to radioiodine, or individuals who choose to avoid permanent hypothyroidism. Ultimately, a patient individualised approach that prioritises early and sustained control of hyperthyroidism will improve long-term outcomes regardless of the therapy modality used. [ABSTRACT FROM AUTHOR]

Background  Thirty-day readmission has become a significant health care metric reflecting the quality of care and on the cost of service delivery. There is little data on the impact of complications following skull base surgery (SBS) on emergency readmission. Identifying modifiable risk factors for readmission may improve care and reduce cost. Design  The study was designed as a single-center retrospective cohort study. Methods  Records for a consecutive series of 165 patients who underwent open or endoscopic SBS by a single surgeon reviewed. Patients with pituitary adenoma were excluded. The diagnosis, procedure, complications, length of stay (LOS), body mass index (BMI), and smoking status were recorded. Readmission to the neurosurgical department or regional hospitals was either noted prospectively or the patient contacted. Cause and length of readmission was documented. Results  Of the 165 cases, 14 (8.5%) were readmitted within 30 days. Causes for readmission included cerebrospinal fluid (CSF) leak in 5/14 or 35.7% (overall rate for readmission for this complication in the series is 3.1%), infection in 4/14 (28.6%), hyponatraemia in 2/14 (14.3%), vascular: sinus thrombosis in 1/14 (7.1%), seizures in 1/14 (7.1%), and epistaxis in 1/14 (7.1%). Initial and readmission LOS was 6 and 14 days, respectively. BMI was higher in those readmitted within 30 days (33.2 kg/m 2) versus no readmission (27.1 kg/m 2). In addition, of those readmitted within 30 days, 35.7% were smokers compared with 20.8% in those not readmitted. Conclusion  In this series, smoking and raised BMI may be indicators for within 30-day readmission and complications in this population, raising the question of risk factor modification prior to elective intervention. [ABSTRACT FROM AUTHOR]

Purpose: Current knowledge of the reasons for patients' preference for rheumatoid arthritis (RA) treatment modes is limited. This study was designed to identify preferences for four treatment modes, and to obtain in-depth information on the reasons for these preferences. Patients and Methods: In this multi-national, cross-sectional, qualitative study, in-depth interviews were conducted with adult patients with RA in the United States, France, Germany, Italy, Spain, Switzerland, the United Kingdom, and Brazil. Patients' strength of preference was evaluated using a 100-point allocation task (0– 100; 100=strongest) across four treatment modes: oral, self-injection, clinic-injection, and infusion. Qualitative descriptive analysis methods were used to identify, characterize, and summarize patterns found in the interview data relating to reasons for these preferences. Results: 100 patients were interviewed (female, 75.0%; mean age, 53.9 years; mean 11.6 years since diagnosis). Among the four treatment modes, oral administration was allocated the highest mean (standard deviation) preference points (47.3 [33.1]) and was ranked first choice by the greatest percentage of patients (57.0%), followed by self-injection (29.7 [27.7]; 29.0%), infusion (15.4 [24.6]; 16.0%), and clinic-injection (7.5 [14.1]; 2.0%). Overall, 56.0% of patients had a "strong" first-choice preference (ie, point allocation ≥ 70); most of these patients chose oral (62.5%) vs self-injection (23.2%), infusion (10.7%), or clinic-injection (3.6%). Speed and/or ease of administration were the most commonly reported reasons for patients choosing oral (52.6%) or self-injection (55.2%). The most common reasons for patients not choosing oral or self-injection were not wanting to take another pill (37.2%) and avoiding pain due to needles (46.5%), respectively. Conclusion: These data report factors important to patients regarding preferences for RA treatment modes. Patients may benefit from discussions with their healthcare professionals and/or patient support groups, regarding RA treatment modes, to facilitate shared decision-making. [ABSTRACT FROM AUTHOR]

Individuals with chronic pain commonly report significant functional impairment and reduced quality of life. Despite this, little is known about psychological processes and mechanisms underpinning enhancements in well-being within this population. The study aimed to investigate whether (1) increased levels of pain intensity and interference were associated with lower levels of mental well-being, (2) increased positive goal engagement was associated with higher levels of mental well-being and (3) whether the relationships between pain characteristics and mental well-being were mediated by increased positive goal engagement. A total of 586 individuals with chronic pain participated in the cross-sectional, online study. Participants completed self-report measures to assess pain intensity and interference, mental well-being and goal motivation variables. Results showed that pain interference and positive goal engagement were associated with mental well-being. Moreover, the relationship between pain interference and mental well-being was partially mediated by positive goal engagement. The results provide tentative evidence for the protective role of positive goal engagement in enabling individuals with chronic pain to maintain a sense of mental well-being. The study develops the biopsychosocial model of chronic pain by examining the roles and relationships of relevant yet previously unexplored psychological constructs. The promotion of mental well-being through the enhancement of positive goal engagement is discussed, offering a platform for further research and clinical interventions. [ABSTRACT FROM AUTHOR]

• Vegetation response to drought can be inferred from correlating VAI and SPEI. • The strongest accumulation period for vegetation response is 6–8 months. • Trees and irrigated cropland are the least sensitive to drought. • Shrubland and rainfed cropland show the most sensitivity to drought. • The cumulative climate has a higher impact on vegetation than lag effects. Drought caused by climate change has significantly increased vegetation vulnerability in Afghanistan during the last decades. This paper investigates vegetation response to drought at multiple scales across the country based on historical data from 1980 to 2020. It explores the multiscale relationships between drought as indicated by the grid-based standardised precipitation evapotranspiration index (SPEI) and vegetation condition as represented by the satellite-derived vegetation anomaly index (VAI). It also examines the links of dominant land cover with drought and their implications for agriculture. We assess the spatiotemporal correlations by integrating TerraClimate grids with timeseries data sourced from NOAA AVHRR (National Oceanic and Atmospheric Administration Advanced Very High-Resolution Radiometer), MODIS (Moderate Resolution Imaging Spectroradiometer) images and ESA CCI (European Space Agency Climate Change Initiative) land cover maps. We evaluated the effect of cumulative drought on predominant land covers. Our results show years 2000–2001 and 2017–2018 as the driest in the last four decades, and vegetation substantially correlated to drought with spatial and temporal variations across Afghanistan. The most sensitive vegetation response months are June to July and the most significant cumulative drought impacts on vegetation are 6 to 8 months. The predominant land covers more prone to negative effects under severe drought are (in order) shrubland, rainfed cropland, grassland, trees, and irrigated cropland. These findings suggest the sensitivity of vegetation to drought that future national scale drought management should be focused on. This study also demonstrates the usefulness of open-access data to researchers and planners in data-poor countries. [ABSTRACT FROM AUTHOR]

Declarations Competing interests Peter Taylor declares that he is Associate Editor of I Thyroid Research i and that the article was assigned to another Editor to assume responsibility for overseeing peer review. Correction to: Age-related variation in thyroid function - a narrative review highlighting important implications for research and clinical practice Peter Taylor declares that he is Associate Editor of I Thyroid Research i and that the article was assigned to another Editor to assume responsibility for overseeing peer review. [Extracted from the article]

As most disease causing pathogens require transmission from an infectious individual to a susceptible individual, continued persistence of the pathogen within the population requires the replenishment of susceptibles through births, immigration, or waning immunity. Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers from infection. If, initially, the prevalence of disease increases (that is, the infection takes off), the number of infectives will usually decrease to a low level after the first major outbreak. During this post-outbreak period, the disease dynamics may be influenced by stochastic effects and there is a non-zero probability that the epidemic will die out. Die out in this period following the first major outbreak is known as an epidemic fade-out. If the disease does not die out, the susceptible population may be replenished by the waning of immunity, and a second wave may start. In this study, we investigate if the rate of waning immunity (and other epidemiological parameters) can be reliably estimated from multiple outbreak data, in which some outbreaks display epidemic fade-out and others do not. We generated synthetic outbreak data from independent simulations of stochastic SIRS models in multiple communities. Some outbreaks faded-out and some did not. We conducted Bayesian parameter estimation under two alternative approaches: independently on each outbreak and under a hierarchical framework. When conducting independent estimation, the waning immunity rate was poorly estimated and biased towards zero when an epidemic fade-out was observed. However, under a hierarchical approach, we obtained more accurate and precise posterior estimates for the rate of waning immunity and other epidemiological parameters. The greatest improvement in estimates was obtained for those communities in which epidemic fade-out was observed. Our findings demonstrate the feasibility and value of adopting a Bayesian hierarchical approach for parameter inference for stochastic epidemic models. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately‐to‐severely active rheumatoid arthritis (RA). Methods: Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long‐term extension study. The data analysis set designated "All‐bari‐RA" included all baricitinib exposures at any dose. Results: Overall, 3,492 RA patients received baricitinib (7,860 patient‐years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient‐years for placebo and 0.8 per 100 patient‐years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient‐years for placebo and 0.5 per 100 patient‐years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient‐years for placebo and 2.4 per 100 patient‐years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo‐controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg–4 mg‐extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient‐years in those receiving 2 mg baricitinib and 0.6 per 100 patient‐years in those receiving 4 mg baricitinib). In the All‐bari‐RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient‐years. Conclusion: In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer‐term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA. [ABSTRACT FROM AUTHOR]

Tofacitinib and baricitinib are the first orally available, small-molecule inhibitors of Janus kinase (JAK) enzymes to be approved for the treatment of RA. Tofacitinib is a selective JAK1, 3 inhibitor with less activity against JAK2 and TYK2 and baricitinib is a selective, oral JAK1, 2 inhibitor with moderate activity against TYK2 and significantly less activity against JAK3. Both drugs have undergone extensive phase III clinical trials in RA and demonstrated rapid improvements in disease activity, function and patient-reported outcomes as well as disease modification. Tofacitinib 5 mg bd, was approved by the Federal Drug Administration in 2012 for the treatment of RA in patients who are intolerant or unresponsive to MTX. An extended release formulation for the treatment of RA was approved by Federal Drug Administration in 2016. In 2017 the European Medicines Agency approved tofacitinib 5 mg bd in combination with MTX and baricitinib 4 mg and 2 mg once daily for the treatment of moderate to severe active RA in adult patients who are intolerant or unresponsive to one or more conventional synthetic DMARDs. [ABSTRACT FROM AUTHOR]

The article focuses on a study which aims at identifying factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA). It mentions introduction of biologic disease-modifying antirheumatic drugs (bDMARD) treatment in RA. It states that an aggressive therapy approach in early RA patients to prevent damage disease progression. It mentions use of methotrexate with glucocorticoids for treating RA.

Using various sources, including the Global Biodiversity Information Facility (GBIF), published literature, recent (2015-2017) collections, as well as bat detector and camera trap surveys with opportunistic sightings and live capture in the upper Okavango catchment in central Angola, we present an updated mammal checklist of 275 species from 15 different orders for Angola (including the Cabinda region). Recent surveys (captures and bat detectors) of small mammals from the upper Okavango catchment yielded 46 species (33 species of bats, ten species of rodents and three species of shrews). One bat (Pipistrellus rusticus, rusty pipistrelle); two rodents (Mus setzeri, Setzer's mouse and Zelotomys woosnami, Woosnam's broad-faced mouse) and one shrew (Suncus varilla, lesser dwarf shrew) were captured for the first time, in Angola. While our species lists of bats conformed to predicted totals, terrestrial small mammals were under sampled, with only 13 species recorded by our trapping survey compared to a total of 42 shrew and rodent species expected based on GBIF records for the central Angolan highlands. Seven terrestrial small mammal species (one shrew and six rodents) are endemic to the central and western Angolan highlands but none of these were captured in our survey. The bat detector surveys added three further bat species to the country list: Pipistrellus hesperidus, Kerivoula argentata, and Mops midas. Camera trap surveys and opportunistic sightings in the upper Okavango catchment in 2016 yielded a total of 35 species of medium-large mammals, from 17 families, although all of these had been reported previously in Angola. GBIF proved to be an excellent source of biodiversity data for Angolan mammals, most importantly for documenting dramatic historical range changes of larger mammals such as the sable (Hippotragus niger niger), Kirk's sable (H. niger kirkii) and the giant sable (H. niger variani). [ABSTRACT FROM AUTHOR]

Introduction: To establish clinical consensus on important and relevant quality-of-care (QoC) attributes in rheumatic disease (RD) treatment that may improve treatment outcomes and guide best practices.Methods: Twenty-three QoC attributes were identified in a literature review. Fifteen European-based clinicians were selected based on their contributions to RD guidelines, publications, and patient care. A three-round (an interview round and two web-based rounds) modified Delphi panel was conducted to reach consensus and finalize a QoC attribute list.Results: In round 1 (clinician interviews), clinicians reported 52 unique QoC attributes across 14 themes, with the greatest number of attributes reported in the “treatment goals” (n = 7) and “remote monitoring” (n = 7) themes. During rounds 2 and 3, the critically important QoC attributes most frequently reported were access to care/treatment (n = 14, 93.3%), safety of treatment (round 2 n = 14, 93.3%, round 3 n = 13, 86.7%), and access to clinicians and specialists (round 2: n = 13, 86.7%, round 3: n = 14, 93.3%). The final list contained 53 QoC attributes.Conclusion: The study demonstrates consensus across several themes of QoC. Quality of care is a complex, multidimensional, and fluid concept that can be improved by ensuring patients have access to care, open communication between patients and clinicians, and the use of novel strategies, such as remote monitoring. Utilization of the attribute list can potentially improve the lives of patients, provide clinicians with tools to provide greater QoC, and improve the healthcare system as a whole.Funding: Merck & Co., Inc. [ABSTRACT FROM AUTHOR]

Vitamin D is a particularly important sterol hormone, with evidence emerging of its beneficial effects well beyond bone. In consequence of this and increased global recognition of vitamin D deficiency in the general population, there has been a resurgence in treatment with vitamin D preparations. However, the increasing use of vitamin D treatments has also seen a substantial increase in the number of reports of vitamin D intoxication, with the majority (75%) of reports published since 2010. Many of these cases are a consequence of inappropriate prescribing, and the use of high‐dose over‐the‐counter preparations or unlicensed preparations. This review highlights that the majority of cases were preventable and discusses the inappropriate use of poorly formulated, and unlicensed vitamin D preparations. [ABSTRACT FROM AUTHOR]

The idea that anthropological climate change is purely a product of modernity (industrialization) is challenged by the contention that such environmental change is many millennia old and is a consequence of urban demand. This argument combines the urban growth theory of Jane Jacobs with the early anthropogenic climate modelling of William Ruddiman and requires a trans-modern sensibility for handling climate change in both theory and practice. We argue for a critical urban geography approach and offer two initial contributions. First, a new urban geographical narrative is constructed to replace the modern progress myth and its top-down political and technological presumptions. Centred on 8,000 years of as the crucial link in the human-environment planetary relation. Second, this leads to suggestions for new 'bottom-up' research agendas, both historical concerning the crucial under-estimation of urban process, and contemporary relating to: the urban demand mechanism, framing a politics of change through cities, and locating cities in the theory of social reproduction. This is an ongoing rethinking exercise that concludes with an invitation to readers to engage and develop this critical research path. urban demand, our alternative narrative highlights everyday consumption activities as the crucial link in the human-environment planetary relation. Second, this leads to suggestions for new 'bottom-up' research agendas, both historical concerning the crucial under-estimation of urban process, and contemporary relating to: the urban demand mechanism, framing a politics of change through cities, and locating cities in the theory of social reproduction. This is an ongoing rethinking exercise that concludes with an invitation to readers to engage and develop this critical research path. [ABSTRACT FROM AUTHOR]

Amaç: Bu çalışmada, 9,3 yıla kadar olan verilerle barisitinibin (BARI; orta ila şiddetli RA için onaylı, oral ve seçici bir JAK1/JAK2 inhibitörü) güvenlilik profili bildirilmektedir. Yöntem: Toplam 9 randomize çalışmanın (5×Faz3, 3×Faz2, 1×Faz1b) ve 1 uzun dönem uzatma (LTE) çalışmasının birleştirilmiş verileri değerlendirilmiştir. İnsidans oranları (IR)/100 risk altındaki hasta yılı (PYR), ≥1 BARI dozuyla tedavi alan tüm hastalar için (Tüm BARI-RA) hesaplanmıştır. Özel öneme sahip AO'lar 48 aylık aralıklarla değerlendirilmiştir. MACE, 5×Faz3 çalışma ve LTE'de karara bağlanmıştır. MACE için IR, ≥1 kardiyovasküler risk faktörü (mevcut sigara kullanımı, hipertansiyon, HDL <40 mg/dL, diyabet veya arteriyosklerotik kardiyovasküler hastalık) bulunan ≥50 yaş grubu hastalardan oluşan alt gruplarda değerlendirilmiştir. SEER17 kullanılarak malignite (NMSC hariç) için standartlaştırılmış bir insidans oranı (SIR) ve genel popülasyon mortalitesi kullanılarak standartlaştırılmış mortalite oranı (SMR) tahmin edilmiştir. VT, PE, DVT/PE için maruziyete göre ayarlanmış IR (EAIR), Tüm BARI-RA genelinde BARI 2-mg/4-mg alanlar için hesaplanmıştır. Bulgular: Toplam 3.770 hasta BARI almış (14,744.4 PYE; medyan maruziyet: 4,6 yıl, maksimum maruziyet: 9,3 yıl); PYE'nin %80,5'inin BARI 4-mg ve %18,1'inin BARI 2-mg grubunda olduğu saptanmıştır. Herhangi bir TEAE ve SAE (ölüm dahil) için EAIR/100 PYE, 22,6 ve 7,4 olarak belirlenmiştir (Tablo 1). IR zaman içinde stabil kalmıştır (Şekil 1). MACE IR (%95 GA), ≥50 yaş grubu hastalar için 0,68 (0,52, 0,88) olarak kaydedilmiştir. MACE IR (%95 GA), ≥1 kardiyovasküler risk faktörü olan ≥50 yaş grubu hastalarda 0,77 (0,56, 1,04) olarak saptanmıştır. SEER17 standardına dayalı olarak NMSC hariç maligniteler için SIR (%95 GA) 1,07 (0,90, 1,26), SMR (%95 GA) ise 0,74 (0,59, 0,92) olarak belirlenmiş; bu bulgu, BARI ile tedavi uygulanan hastalarda malignite ve ölüm insidansının genel ABD popülasyonuna benzer olduğunu göstermiştir. BARI 2-mg (PYE=2678) ve BARI 4-mg (PYE=11,872) alan hastalarda EAIR (%95 GA), DVT için 0,41 (0,21, 0,73) ve 0,35 (0,25, 0,48); PE için 0,26 (0,11, 0,54) ve 0,27 (0,18, 0,38); DVT/PE için 0,49 (0,26, 0,83) ve 0,51 (0,39, 0,66) olarak belirlenmiştir. Sonuç: BARI, daha önce bildirilene benzer bir güvenlilik profilini korumuş ve 14,744 PYE ile 9,3 yıla kadar maruziyet kapsamında güvenlilik olaylarında herhangi bir IR artışı görülmemiştir. [ABSTRACT FROM AUTHOR]

Mapping and tracking invasive alien plant species (IAPS) and their invasiveness can be achieved using remote sensing (RS) and geographic information systems (GIS). Continuous monitoring using RS, GIS and modelling are fundamental tools for informing invasion and management strategies. Using systematic comparisons, we look at three remote sensing imagery platforms and how accurately they can be classified within the Vhembe biosphere reserve, Limpopo Province, South Africa. Supervised classification of National Geospatial Information Colour Digital Aerial Imagery, DigitalGlobe Worldview 2 and CNES SPOT 6 was performed. The Spectral Angle Mapper (SAM) algorithm was used to identify the best satellite for species-level classification. The accuracy of the classifications produced an overall accuracy (OA) of 71% with a Kappa coefficient (KC) of 0.76 for CDA photographs, an OA of 81% and a KC of 0.80 for Worldview 2, and an OA of 89% with a KC of 0.86 for SPOT 6 imagery. Therefore, SPOT 6 imagery came out as the most suitable for species-level classification. The classification results from the SPOT 6 imagery were used as input data for further species distribution modelling of Mauritius Thorn and River Red Gum in the VBR. [ABSTRACT FROM AUTHOR]

I review recent results concerning the relationship between the inclusive fitness (IF) effect and standard measures of allele fitness in a finite-population, with attention to the effect of heterogeneity in population structure and nonadditive fitness effects. In both cases, existing theoretical work is somewhat technical and I try to provide a more transparent account. In a heterogeneous population it is known that inclusive fitness will generally fail to incorporate the effects of selection on the distribution of alleles among states unless a reproductive-value weighting is used. But even given that, recent work shows that under certain updating rules, the IF effect can fail to be equivalent to standard measures such as fixation probability. In terms of synergistic fitness effects, I review the result that in the finite population model, the IF effect can be calculated using only 'additive' relatedness coefficients so that computational difficulties found in the infinite-population model do not arise. In my own work, there is an interaction here in that my 2012 work on synergy with Maciejewski made an assumption about inclusive fitness that my 2014 work on heterogeneity with Tarnita showed to be wrong. I include (Appendix C) a corrected argument for the 2012 result. [ABSTRACT FROM AUTHOR]

Our basic argument is that we should be thinking in trans-modern ways when considering how to react to anthropogenic climate change. Showing that mainstream approaches to climate change theory and policymaking are overtly modern, we identify this as a mindscape inherently constrained by its particular chronology and chorography. Our contribution to necessary trans-modern thinking is a presentation of eleven basic and widely accepted theses on modern chronology and chorography that we contest through antitheses, which we argue are more suited to engaging with anthropogenic climate change. These support a consumption argument for urban demand being the crucial generator of climate for 8,000 years in direct contradiction to the production argument that greenhouse gases are the crucial generator of climate change for 200 years. The modern policymaking focus on curbing carbon emissions is thus fundamentally flawed - merely feeding energy for continuing an accelerating global consumption in a different way that is only marginally more climate-friendly. Reflecting on the antitheses, we conclude by discussing the difficulties of translating trans-modern ideas into political action. [ABSTRACT FROM AUTHOR]

Background: Although the majority of thyroid nodules are benign the process of excluding malignancy is challenging and sometimes involves unnecessary surgical procedures. We explored the development of a predictive model for malignancy in thyroid nodules by integrating a combination of simple demographic, biochemical, and ultrasound characteristics. Methods: Retrospective case-record review. We reviewed records of patients with thyroid nodules referred to our institution from 2004 to 2011 (n = 536; female 84 %, mean age 51 years). All malignancy was proven histologically while benign disease was either confirmed histologically, or on cytology with minimum 36-month observation period. We focused on the following predictors: age, sex, smoking status, thyroid hormones (FT4 and TSH) and nodule characteristics on ultrasound. Variables were included in a multivariate logistic regression and bootstrap analyses were used to confirm results. Results: Independent predictors of malignancy in the fully adjusted model were TSH (OR 1.53, 95 % CI 1.10, 2.12, p=0.01), male gender (OR 3.45, 95 % CI 1.33, 8.92, p = 0.01), microcalcifications (OR 6.32, 95 % CI 2.82, 14.1, p < 0.001), and irregular nodule margins (OR 5.45, 95 % CI 1.61, 18.6, p = 0.006) Bootstrap analyses strengthened these associations and a parsimonious analysis consisting of these variables and age-group demonstrated an area under the curve of 0.77. A predictive score was sensitive (86.9 %) at low scores and highly specific (94.87 %) at higher scores for distinguishing benign from malignant disease. Conclusions: A predictive model for malignancy using a combination of clinical, biochemical, and radiological characteristics may support clinicians in reducing unnecessary invasive procedures in patients with thyroid nodules. [ABSTRACT FROM AUTHOR]

Background: "Anarchic hand" is a rare condition characterised by non-volitional, goal-directed movements of one arm. We report a case with analysis of structural and functional connectivity.Case Presentation: A 15 year old girl developed intermittent symptoms of intermanual conflict or anarchic hand as a result of traumatic brain injury during which she sustained a callosal bleed. Resting-state fMRI and DTI tractography were performed at a stage when symptoms had largely resolved.Conclusion: Structural connectivity between homologous superior frontal areas and functional connectivity between homologous posterior cingulate areas were significantly reduced, which may have contributed to causation. Tractography demonstrated new indirect connections between supplementary motor areas via the cerebellum, which we propose contributed to symptom resolution. [ABSTRACT FROM AUTHOR]