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Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation—whereby probabilistic within-host distributions are cast as expected population-level proportions—we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity—and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values—our model provides insights into important, but poorly understood, epidemiological features of P. vivax. [ABSTRACT FROM AUTHOR]

Hosting 1460 plant and 126 vertebrate endemic species, the Great Escarpment (hereafter, Escarpment) forms a semi‐circular "amphitheater" of mountains girdling southern Africa from arid west to temperate east. Since arid and temperate biota are usually studied separately, earlier studies overlooked the biogeographical importance of the Escarpment as a whole. Bats disperse more widely than other mammalian taxa, with related species and intraspecific lineages occupying both arid and temperate highlands of the Escarpment, providing an excellent model to address this knowledge gap. We investigated patterns of speciation and micro‐endemism from modeled past, present, and future distributions in six clades of southern African bats from three families (Rhinolophidae, Cistugidae, and Vespertilionidae) having different crown ages (Pleistocene to Miocene) and biome affiliations (temperate to arid). We estimated mtDNA relaxed clock dates of key divergence events across the six clades in relation both to biogeographical features and patterns of phenotypic variation in crania, bacula and echolocation calls. In horseshoe bats (Rhinolophidae), both the western and eastern "arms" of the Escarpment have facilitated dispersals from the Afrotropics into southern Africa. Pleistocene and pre‐Pleistocene "species pumps" and temperate refugia explained observed patterns of speciation, intraspecific divergence and, in two cases, mtDNA introgression. The Maloti‐Drakensberg is a center of micro‐endemism for bats, housing three newly described or undescribed species. Vicariance across biogeographic barriers gave rise to 29 micro‐endemic species and intraspecific lineages whose distributions were congruent with those identified in other phytogeographic and zoogeographic studies. Although Köppen–Geiger climate models predict a widespread replacement of current temperate ecosystems in southern Africa by tropical or arid ecosystems by 2070–2100, future climate Maxent models for 13 bat species (all but one of those analyzed above) showed minimal range changes in temperate species from the eastern Escarpment by 2070, possibly due to the buffering effect of mountains to climate change. [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]

Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib. [ABSTRACT FROM AUTHOR]

Morphometric studies of 3D micro CT‐scanned images can provide insights into the evolution of the brain and sensory structures but such data are still scarce for the most diverse mammalian order of rodents. From reviewed and new data, we tested for convergence to extreme aridity and high elevation in the sensory and brain morphology of rodents, from morphometric data from micro‐CT X‐ray scans of 174 crania of 16 species of three distantly related African murid (soft‐furred mice, Praomyini, laminate‐toothed rats, Otomyini, and gerbils, Gerbillinae) clades and one North American cricetid (deer mice and white‐footed mice, Peromyscus) clade. Recent studies demonstrated convergent evolution acting on the oval window area of the cochlea (enlarged in extremely arid‐adapted species of Otomyini and Gerbillinae) and on endocranial volume (reduced in high elevation taxa of Otomyini and Peromyscus). However, contrary to our predictions, we did not find evidence of convergence in brain structure to aridity, or in the olfactory/respiratory system (turbinate bones) to high elevation. Brain structure differed, particularly in the petrosal lobules of the cerebellum and the olfactory bulbs, between Otomyini and Gerbillinae, with extreme arid‐adapted species in each clade being highly divergent (not convergent) from other species in the same clade. We observed greater "packing" of the maxillary turbinate bones, which have important respiratory functions, in Peromyscus mice from high and low elevations compared to the high‐elevation African Praomyini, but more complex patterns within Peromyscus, probably related to trade‐offs in respiratory physiology and heat exchange in the nasal epithelium associated with high‐elevation adaptation. [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]

In this paper, we consider the occupancy distribution for an open network of infinite server queues with multivariate batch arrivals following a non-homogeneous Poisson process, and general service time distributions. We derive a probability generating function for the transient occupancy distribution of the network and prove that it is necessary and sufficient for ergodicity that the expected occupancy time for each batch be finite. Further, we recover recurrence relations for the transient probability mass function formulated in terms of a distribution obtained by compounding the batch size with a multinomial distribution. [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]

Summary: Motivation: Universal challenges require collective responsibility for identifying future pathways and solutions, unprecedented levels of global co‐operation and a clear set of principles and norms to shape needed actions and responses. In a changing landscape of actors, the norms that have previously evolved and served the interests of one particular group of actors may no longer be fit for purpose. Purpose: The article explores questions about how and why different societal actors and stakeholders are shaping and informing development co‐operation norms, and whether newer members of a growing community of development aid providers will want to sit at an existing table, or go their own way, individually or with other collectives. Methods and approach: The article responds to these questions by drawing on existing literature, and offering an analysis of past, present, and possible future directions for the emergence of international development norms and supernorms. Building on this analysis, it casts forward, to examine the role of new actors and the emergence of new norms, paying particular attention to South–South development co‐operation. Findings: The article proposes a series of challenges and choices which may determine future pathways for current and emerging international development norms. It concludes that emerging donors can challenge or co‐operate with existing norms, while traditional donors must decide how to react to the emergence of other development actors: to contest, or to co‐ordinate and co‐operate through the emergence of new norms which are created and agreed to by both old and new actors. Policy implications: Future processes of negotiation will require dedicated policy spaces in which global actors can negotiate and contest new norms in a shared quest to secure their position in the complex, ever‐shifting landscape of international co‐operation arrangements. [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]

Daily levothyroxine (LT4) is the standard of care for the treatment of hypothyroidism; however, a small number of patients experience residual symptoms of hypothyroidism. Guidelines indicate that a trial with LT4 and liothyronine (LT3) could be attempted once other conditions have been addressed or excluded. Even so, currently, treatment of hypothyroidism can still be suboptimal. [ABSTRACT FROM AUTHOR]

We have investigated the structure and spectra (NMR, UV/visible) of several Yariv reagents and models for these species, using both density functional theory (DFT) and approximate coupled‐cluster methods (ADC(2)). We have also studied the formation of dimers and model trimers as a first step to understand the aggregation of these species in aqueous solution. One question that our calculations help resolve is the origin of two strong bands in the visible region of the spectrum: these are confirmed as resulting from enol‐keto tautomerism, and are not a result of aggregation, which was a hypothesis that had been advanced previously. The UV/visible spectrum of the Yariv reagents can be explained entirely in terms of tautomerism within a single molecule – no dimers or clusters are involved. [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]

Anthropogenic climate change is a complex process that does not respect political boundaries. Thus it is argued states are problematic agencies for tackling the global climate emergency. But it is the world political map that provides the geographical ontology foundation of the massive efforts of climate policy development. Geography's long tradition of regional study is suggested as a means of countering focus on states for policy development. Ontological inventions are proposed that transcend states. These take the form of experimenting with geographical regions encompassing human‐environmental interactions as alternative spatial policy framings to the world political map. Three examples are presented: intergovernmental resilient regions for mitigation; localization through urban sustainable regions; and regions for planetary stewardship of humans‐in‐nature. None of these are 'solutions', rather they are illustrations of possible future regional geographies intended to stimulate current cohorts of geographers to contribute necessary regional thinking to the scholarship unpinning climate change policymaking. [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]

Ten years ago, the genus-level and species-level taxonomy of African pipistrelloid bats was in a state of flux. In spite of advances in the past decade, gaps in collecting from species-rich regions like Angola have hampered efforts to revise this group. We report on new collections of pipistrelle-like bats from the poorly sampled central highlands of Angola (1000–1500 m a.s.l.) as well as comparative material from lower-lying areas of Eswatini and South Africa. Specimens identified as Neoromicia anchietae , collected 400–700 km east of the holotype locality in the western highlands of Angola, were genetically and morphologically distinctive from N. anchietae s.l. from South Africa and Eswatini. We describe herein this latter lineage as a distinct species from low-lying areas of south-eastern Africa, distinct from N. anchietae s.s. , which is therefore restricted to the central and western Angolan highlands. We also identified shallow to deep genetic divergence between different African regions in other recognized pipistrelloid species, such as conspecificity between the long-eared species Laephotis angolensis from Angola and Laephotis botswanae from northern Botswana, northern Namibia and south-western Zambia. Our phylogeny supports a recently proposed generic classification of African pipistrelloid bats. [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]

Aims: There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control. Methods: We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmol/mol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation. Results: There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median = £289 (IQR 247–343) range £31.1–£1713. Higher total expenditure was not associated with improved glycaemic control B(std) = −0.01 (95%CI –0.01, 0.002) p = 0.13. High‐spend practices spent more on SGLT2 inhibitors (16 vs. 9% p < 0.001) and GLP‐1 agonists (13 vs. 11% p < 0.001) and less on insulin (34 vs. 42% p < 0.001), biguanides (9 vs. 11% p = 0.001) and sulphonylureas (2 vs. 3% p < 0.001) than low spend practices. There were no differences in the pattern of drug prescribing between high spend practices with better glycaemic control (mean 68% of patients HbA1c <59 mmol/mol) and those with less good metabolic control (mean 58% of patients HbA1c <59 mmol/mol). Conclusions: Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications. [ABSTRACT FROM AUTHOR]

Evaluate relationships between changes in dermatologic assessments and quality of life (QoL) measures; quantify dermatologic symptom severity impacts on QoL in patients with psoriatic arthritis (PsA) treated with tofacitinib. Data were from two phase III studies; patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg every other week, or placebo advancing to tofacitinib 5 or 10 mg BID at Month 3. Repeated measures longitudinal models assessed relationships between dermatologic assessments (predictors) Itch Severity Item (ISI), Physician's Global Assessment of Psoriasis (PGA-PsO), and Patient's Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question (PGJS-VAS-PsO), and QoL measures (outcomes) Dermatology Life Quality Index (DLQI) and Short Form-36 Health Survey Version 2 (SF-36v2). Models included one predictor and one outcome. Direct, approximately linear relationships existed between predictors and outcomes. ISI/PGA-PsO/PGJS-VAS-PsO improvements from baseline of ≥3/≥2/≥40-mm VAS corresponded with clinically meaningful DLQI improvements; improvements from baseline of ≥4/≥3/≥40-mm VAS generally corresponded with clinically meaningful improvements across component scores and all SF-36v2 domains. Substantial links exist between dermatologic symptoms and QoL in patients with PsA, potentially informing patient-centered care and research. Rheumatologists should be aware of dermatologic manifestations and QoL impacts in patients with PsA. NCT01877668; NCT01882439 [ABSTRACT FROM AUTHOR]

The three different engagements with my geographical ontology proposition each produce equally relevant additions to the argument. There are interesting discussions of data needs, geographical synthesis and confronting policy differences. Their common thread is recognition of the inherent complexities facing climate policy making. [ABSTRACT FROM AUTHOR]

Manuel Castells has been a leading figure in urban studies since the 1970s and is widely acclaimed for combining Marxist theoretical thinking with practical policy proposals. As a social theorist, his particular focus on the spatiality of cities has led to him becoming very influential in urban geography as specifically evidenced by his two invited papers in TESG in 1993 and 2002. In this paper, we develop an ontological critique of Castells' employing the mainstream position that cities reflect the nature of the societies that encompasses them, whereas we consider cities as the makers of their encompassing society. The TESG papers are broadly reviewed by contrasting their governance/policy approach with Jane Jacobs' economics/development approach. This critique does not diminish our appreciation for Castells' contribution to urban studies, rather the ontological critique is used as a tool for providing clarity of scholarship, not another episode of academic squabbling in urban studies. [ABSTRACT FROM AUTHOR]

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]

Since entering the clinic 25 years ago, biologic TNF inhibitors have transformed the outlook for people with rheumatoid arthritis and set the standard for all other targeted therapies. Despite changes to the therapeutic landscape, TNF inhibitors look set to remain an important treatment option for the foreseeable future. [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]

London and New York are the leading cities in the world of corporate globalisation: their financial, professional, and creative services are at the centre of the commercial connections that constitute the world city network. The relations between the two cities are more complementary than competitive, commonly indicated by the concept of NY‐LON as a trans‐oceanic service conglomerate for facilitating economic globalisation. However, world city network analysis shows London growing its overall servicing connectivity more than New York. This change in the inter‐city relation is investigated through focus on the service connectivity and agglomeration capacities of the two cities. It is found that they share a very similar connectivity regional profile while simultaneously showing stark differences in their service agglomeration sector profiles. This is shown to be the result of London gaining the rapidly growing super‐rich servicing market. Thus while New York continues its long‐term production of financial innovations, London has grown an offshore platform for global capital specifically in the form of the world's money management centre. [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]

We argue that Geography should be centre stage for understanding today's climate emergency. It warrants this position because as a field of study it uniquely straddles physical/environmental and human/social scholarships. In the wider academic world, bringing together scholars across this "cultural" divide has traditionally been difficult, and continues to be so in current responses to human‐induced climate change. Specifically, physical scholarship and science dominate at the expense of social scholarship and science. But it is now widely recognised we are living in a time of climate emergency and this simply will not do. Geography as a field of study that bridges these two forms of knowledge has the potential to become strategically relevant in this situation. The concept of risk that links environment and people from the Natural Hazards paradigm is identified as a way in which a holistic Geography can take an important lead in worldwide scholarly inputs into anthropogenic climate change understanding and consequent policy development. Geography as a field of study can provide a bridging link between physical science and social science contributions to understanding anthropogenic climate change. The paper discusses how and why this might come about. [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]

Methylketene (CH 3 CHCO) and acrolein (CH 2 CHCHO) have received considerable attention from both theoreticians and experimentalists. In a number of computational studies, it has been identified that both isomers sit alongside their dissociation products C 2 H 4 + CO , at the bottom of the potential energy surface with energies very close to each another. The most striking feature from preliminary calculations is that the relative energy difference between methylketene and trans-acrolein ( Δ E 0.8–3.4 kJ/mol) changes with respect to choice of reference geometry, correlation treatment, and basis set expansion. While the thermodynamic profile favours trans-acrolein as the lowest-lying isomer, it is difficult to estimate the quality of the currently available results, which are determined with a variety of methods. At higher levels of theory together with reducing basis set incompleteness methylketene might be the true minimum on the C 3 H 4 O potential energy surface. In addition to their being almost isoenergetic, much interest in these C 3 H 4 O isomers stems from an astrochemical standpoint. The discovery of both cis and trans-acrolein in the interstellar medium has led to speculation that methylketene may also be present. While thermodynamically methylketene proves to be a good candidate for extra-terrestrial observation, as yet there have been no reports of its detection. To this end, by applying the best correlation treatment that has been used for this species, using by far the most elaborate and accurate basis sets (up to sextuple-zeta quality), we establish the relative ordering and energetic difference between methylketene and trans-acrolein to within chemical accuracy (within 1 kJ/mol). We find the inclusion of zero-point energy, explicit core-correlation, and augmentation with diffuse functions have significant effects in determining the relative energy difference of the isomers, and assignment of the C 3 H 4 O global minimum. [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]

To date, four $ \hbox {C}_2\hbox {H}_4\hbox {O}_2 $ C 2 H 4 O 2 isomers have been identified in the interstellar medium: acetic acid, glycolaldehyde, methyl formate, and (Z)-1,2-ethenediol. The detection of these species raises the question of whether other related carbohydrates could be present in similar astrophysical environments. In this study, we report a systematic investigation of six $ \hbox {C}_2\hbox {H}_4\hbox {O}_2 $ C 2 H 4 O 2 isomers not previously observed spectroscopically in space: anti-(1)-, (2)- and (3)- $ \hbox {CH}_2=\hbox {CHOOH} $ CH 2 = CHOOH , methyldioxirane, and anti- and syn-(2S)-oxiran-2-ol. For each species, we employ coupled-cluster theory at the AE-CCSD(T)/cc-pCVQZ level to provide accurate equilibrium parameters, rotational constants, quartic centrifugal distortion parameters, and permanent electric dipole moment components. Anharmonic force fields were determined within vibrational perturbation theory to second order and evaluated using the MP2 method, thus allowing the evaluation of vibrational corrections. These computations provided, as a by-product, sextic centrifugal distortion constants. Rotational spectra have subsequently been simulated in the millimeter/submillimeter-wave frequency for the first time. It is hoped and anticipated that the accurate theoretical rovibrational spectral data presented herein will aid in experimental investigations of these title molecules in the interstellar medium. [ABSTRACT FROM AUTHOR]

Introduction: Recent prescribing policies in England and Wales have imposed significant restrictions on liothyronine prescribing in general practice driven by the prohibitive costs and uncertain benefits of liothyronine in the management of hypothyroidism. However, the impact of these policies on liothyronine usage and costs is still unclear. Methods: Data were downloaded from the NHS monthly General Practice Prescribing Data in England and from the Comparative Analysis System for Prescribing Audit (CASPA) in Wales for 2011–2020. Trends over the period in amount and costs of levothyroxine and liothyronine prescribing were analysed. Results: The total medication costs per year for England Wales for hypothyroidism rose from £60.8 million to £129.8 million in 2015–16 and have since reduced to £88.4 million. Levothyroxine prescriptions have been growing above the population growth rate at 0.7%/annum in England and 1.1% in Wales. The costs/patient/year for liothyronine rose from £550 to £3000 in 2015–16 and has since fallen to £2500. Use of liothyronine as a percentage of levothyroxine started to fall in 2015–16 at 7%/annum in England and 3% in Wales. Nevertheless, 0.5% of levothyroxine‐treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019–20. Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice, a significant number of patients continue to receive this therapy. The price differential of liothyronine vs levothyroxine should be examined again in light of the continuing use of liothyronine. [ABSTRACT FROM AUTHOR]

Objectives: The way that individuals perceive themselves and others may be relevant in understanding difficulties with self‐harm. Repertory grids provide a relatively underutilized means of investigating self‐concept in people who self‐harm. This study aimed to examine the association between self‐concept, captured through a repertory grid method, and self‐harm. Method: Ninety‐eight participants with a history of self‐harm took part in the study. A repertory grid was used to derive distances between four elements ('current self', 'ideal self', 'self‐harming self', and 'others who self‐harm'). Associations between these distances and measures of self‐harm behaviour, well‐being and perceived recovery, were estimated. Results: Repertory grid distances were significantly associated with self‐harm. When adjusting for covariates, self‐harm in the past year was positively associated with a greater distance (or less perceived similarity) between current and ideal self, and a smaller distance (greater perceived similarity) between current self and others who self‐harm. Repertory grid distances were also associated with well‐being and perceived recovery. Conclusions: The results are consistent with the idea that self‐perception is associated with self‐harm and related difficulties. The results also highlight the potential utility of repertory grids as a tool for exploring self‐concept. The cross‐sectional nature of the study precludes inferences about directionality or the temporal characteristics of associations. Practitioner points: More recent experiences of self‐harm may be reflected in the way individuals perceive or construe themselves.The way in which individuals who self‐harm perceive or construe themselves may also be related to their current well‐being and perceived recovery.Repertory grids may be a useful tool in clinical practice for investigating self‐concept in those who self‐harm.Repertory grids may provide a more idiographic, clinical outcome assessment in those who self‐harm. [ABSTRACT FROM AUTHOR]

We investigate the behavior of equilibria in an M/M/1 feedback queue where price- and time-sensitive customers are homogeneous with respect to service valuation and cost per unit time of waiting. Upon arrival, customers can observe the number of customers in the system and then decide to join or to balk. Customers are served in order of arrival. After being served, each customer either successfully completes the service and departs the system with probability q, or the service fails and the customer immediately joins the end of the queue to wait to be served again until she successfully completes it. We analyze this decision problem as a noncooperative game among the customers. We show that there exists a unique symmetric Nash equilibrium threshold strategy. We then prove that the symmetric Nash equilibrium threshold strategy is evolutionarily stable. Moreover, if we relax the strategy restrictions by allowing customers to renege, in the new Nash equilibrium, customers have a greater incentive to join. However, this does not necessarily increase the equilibrium expected payoff, and for some parameter values, it decreases it. [ABSTRACT FROM AUTHOR]

12 Söderqvist, T. (1996) Existential projects and existential choice in science: science biography as an edifying genre, in: M. Shortland and R Yeo (Eds) Telling Lives in Science: Essays on Scientific Biography, pp. 45 - 84 (Cambridge: Cambridge University Press). Many people who went on to become scholars and writers about technoscience in its social context, that is, to become contributors to the field now called Science and Technology Studies (STS), were involved in or influenced by counter-cultural and radical activities from the late 1960s, '70s and '80s. Limits of the Forum and the Necessity of (Future) STS Work Importantly, this forum provides only a partial account of the movement from radical science to STS. Further, the essays foreground the importance of counterculture endeavors, including the radical science movement, in developing critical analysis of technoscience within STS. [Extracted from the article]

Taylor proposes the question, "How do we make sense of radical scientists and critics of science in relation to their changing contexts?" After identifying individuals who came to STS after being involved in popular movements of the 1970s, contesting the directions taken in science and technology, he proposes three themes to guide inquiry into the question: transitions, transversals, and tensions. Each of these themes illustrate how different directions (resistance, revival, resignation, ramifications, regularities, reframing), marked shifts in the focus of the intellectual work and lives for some (or perhaps many) of those individuals. These transitions can be seen as linked into a transversal project of exploring ways to stimulate researchers (and students training to become researchers) to self-consciously examine the complexity of their social situatedness so as to change the ways they address the complexity of the situations they study. [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]

An editorial is presented to the article cognitive analytic therapy (CAT) has become a popular psychotherapeutic approach for working with mental and physical health difficulties. Topics include a notable characteristic of CAT research to date is that it has largely consisted of practice based evidence; and case series and small-scale pilot trials represent an essential step in determining the acceptability.

Background: Brief psychological therapies may be helpful for people who have recently self‐harmed. The current paper reports on a service evaluation of a novel brief therapy service based within an Emergency Department, Hospital Outpatient Psychotherapy Engagement (HOPE) Service. This service combines elements of psychodynamic interpersonal and cognitive analytic therapy to help people who present with self‐harm‐related difficulties. The primary aim of this service evaluation was to ascertain the feasibility of HOPE in terms of attendance rates. The study also examined variables associated with engagement, and change over time in psychological distress for those attending the service. Method: The HOPE service was evaluated over a ten‐month period. Consenting patients completed measures of psychological distress and working alliance across four therapy sessions and one follow‐up session. Measures of emotion regulation style and self‐harm function were also completed at the point of referral. Results: Eight‐nine patients were referred to the service (83 eligible referrals). Fifty‐three (64%) attended at least one therapy session. Baseline variables did not distinguish people who attended and people who did not. Psychological distress decreased significantly across the sessions. Most people reported a good working alliance with their therapist. Conclusions: The results of this service evaluation support the feasibility of the HOPE service, demonstrating good engagement rates given the complexity of the population and context. Whilst there was evidence of reductions in distress, randomized controlled trials are needed to determine if HOPE has clinical efficacy. Practitioner points: Rates of engagement with HOPE suggest the service is feasible in an Emergency Department contextWorking alliance scores were positive for the majority of patientsThe HOPE service shows promise as a brief intervention for people who self‐harm but requires further evaluationRandomized controlled trials are needed to determine the clinical efficacy of the HOPE service [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]

Drawing on an autoethnographic inquiry we present a first-person, narrative account of a mathematics teacher's experience of developing an ethically responsible teaching practice. Reflective commentary on narrative vignettes illustrates the teacher's inquiry in the role of researcher as transformative learner. Inspired by transformative learning theory, he engaged in critical self-reflection on his moments of teaching, which prompted him to switch from the teacher's point of view and pay heed to his student's meaning perspective. This transformation of perspective enabled him to avoid conflict by negotiating a deal with the young resistant learner – 'a rebel kid' – to generate mutual respect, focus on values, and successfully adjust to the student's learning trajectory. The result of this inquiry suggests that endeavouring to teach from students' points of view is important not only for engaging meaningfully in an educative relationship but also for enhancing the sense of ethical responsibility of both teachers and students. [ABSTRACT FROM AUTHOR]

The African rodent genus Mastomys contains eight species, some of which are widely distributed pest species and others which have restricted distribution. Most species are recognized only on chromosomal or molecular genetic data. We aimed to clarify the systematic status, geographical distribution, and phylogenetic relationships of three Mastomys species occurring in the Okavango Basin and surrounding arid habitats in southwestern Africa, with a focus on the poorly known and questionably valid taxon, Mastomys shortridgei. We described three genetically, morphologically, and ecologically distinct species of Mastomys and documented their respective karyotypes: Mastomys coucha (2n = 36, aFN = 56); Mastomys natalensis (2n = 32, aFN = 54); and M. shortridgei (2n = 36, aFN = 46). The chromosomal differences between M. coucha and M. shortridgei are probably due to pericentric inversions. The time to the most recent common ancestor of all M. coucha and M. shortridgei was estimated at 0.64 (0.30–1.22) Mya. The three species differed significantly from each other in 11 cranial measurements; a discriminant function allowed us to distinguish co‐occurring M. natalensis from M. shortridgei with 95% accuracy. We propose a model to explain the recent peripatric speciation of M. shortridgei from M. coucha based on drainage evolution in south‐central Africa since the Pleistocene. The conservation status of M. shortridgei needs to be re‐evaluated because of its low population densities, restrictive habitat preference, declining habitat quality, and historical and predicted future declines in area of occupancy. [ABSTRACT FROM AUTHOR]