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BACKGROUND Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS This case describes a specific constellation of speech-motor and written language symptoms—apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia—which the authors theorize may be attributable to disruption of a single process of “motor-phonological sequencing.” The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

The Anglo-Israel Colloquium in November 2019, Jerusalem, was a collaboration including Jewish and Arab-Israelis, Palestinians, and British participants arranged to drive forward the agenda for addressing inequalities within our populations as they age. This Colloquium brought together scholars, policy-makers, and service providers in the field of ageing from the UK and from Israel, in order to critically examine the societal effects and implications of both individual and population ageing. The following statement on ageing is the first result. Held up in its wider dissemination by the subsequent pandemic of 2020/2021, we are now delighted that the Jerusalem Declaration is now simultaneously published in Hebrew (Harper, S., & Doron, I. (2021). The Jerusalem Declaration. Gerontology & Geriatrics, 48(1), 113–116. [Hebrew]) and here in the Journal of Population Ageing in both English and Arabic.

Review of: Field trip for one: Self-directed learning with the #MetKids website #MetKids, The Metropolitan Museum of Art (2015) https://www.metmuseum.org/art/online-features/metkids/

This chapter describes presentations in pain medicine which are caused by a mixture of nociceptive, neuropathic, and visceral mechanisms. These include acute pain in surgical and non-surgical patients, chronic post-surgical pain, erythromelalgia, headaches, human immunodeficiency virus, orofacial pain, the specifics of paediatric pain and pain in the elderly, pain related to sickle cell disease, and vascular insufficiency pain.

THE EXPECTATION FOR PARTICIPATORY ARTS TO EFFECTIVELY ENGAGE TARGETED COMMUNITIES MIGHT LEAD TO THE CONCLUSION THAT NON-PARTICIPATION IS FAILURE. BUT IS IT NECESSARILY FAILURE? FOR ARTISTS NAVIGATING “ENTANGLED TERRITORIES” (HALVORSEN, 2017) AND “COMPETING NARRATIVES” (THOMPSON, 2009) IN THE MULTI-CULTURAL PARIS BANLIEUE, NON-PARTICIPATION OR REFUSAL IS AN INEVITABILITY THAT NEEDS TO BE EMBRACED. DRAWING ON THEORIES OF PARTICIPATION FROM THE FIELDS OF SOCIALLY ENGAGED PERFORMANCE, SOCIOLOGY, GEOGRAPHY AND CULTURAL STUDIES, THIS ARTICLE EXPLORES THE VALUE AND NUANCES OF INVISIBLE, MINIMAL, PERIPHERAL OR CONDITIONAL PARTICIPATION ENCOUNTERED IN THE NARROW SPACES FOR MANOEUVRE BETWEEN STAKEHOLDERS’ CONFLICTING AGENDAS. IT ARGUES THAT REFUSALS DO NOT NECESSARILY NEGATE THE WORK, AND THAT ATTENDING TO, AND REDEFINING, THESE MOMENTS MAY BE KEY TO UNDERSTANDING NOT ‘HOW TO GET PEOPLE TO PARTICIPATE BETTER’, BUT HOW TO PERCEIVE NON-PARTICIPATION AS AN ELOQUENT AFFIRMATION OF AGENCY AND A SIGNIFICANT PARTICIPATION IN SOMETHING ELSE.

Although substantial variability is observed in the articulatory implementation of the constriction gestures involved in /ɹ/ production, studies of articulatory-acoustic relations in /ɹ/ have largely ignored the potential for subtle variation in the implementation of these gestures to affect salient acoustic dimensions. This study examines how variation in the articulation of American English /ɹ/ influences the relative sensitivity of the third formant to variation in palatal, pharyngeal, and labial constriction degree. Simultaneously recorded articulatory and acoustic data from six speakers in the USC-TIMIT corpus was analyzed to determine how variation in the implementation of each constriction across tokens of /ɹ/ relates to variation in third formant values. Results show that third formant values are differentially affected by constriction degree for the different constrictions used to produce /ɹ/. Additionally, interspeaker variation is observed in the relative effect of different constriction gestures on third formant values, most notably in a division between speakers exhibiting relatively equal effects of palatal and pharyngeal constriction degree on F3 and speakers exhibiting a stronger palatal effect. This division among speakers mirrors interspeaker differences in mean constriction length and location, suggesting that individual differences in /ɹ/ production lead to variation in articulatory-acoustic relations.

Individual differences are robustly attested in both speech production and perception, with interspeaker variation in production frequently observed in the same domains in which extensive variation is observed across listeners in perception. This study extends existing research by examining whether the relationship between production variability and perceptual sensitivity previously observed for vowels (e.g., Perkell et al., 2008; Franken et al., 2017) is also observed for consonants. 55 speakers of American English completed two online tasks designed to evaluate individual differences in the production and perception of /s/ and /ɹ/: a sentence production task and a 4IAX perceptual discrimination task. Preliminary comparison of acoustic variability measurements from the production task and response accuracy measurements from the perception task suggest that individual differences in these two domains are sometimes, but not always, related across speakers. Specifically, production variability and perceptual sensitivity were correlated for phonologically meaningful acoustic dimensions in the liquid phoneme /ɹ/, but not for any measured dimensions in the fricative phoneme /s/.

Pregnancy has profound effects on a variety of body systems by way of hormonal and physical changes. Many of these changes directly affect body systems involved in singing. Assumptions exist about what can happen to a person's voice during pregnancy, but these assumptions are based on theoretical predictions leaving little knowledge of the lived experiences of voice changes during pregnancy. An anonymous mixed-method survey was given to 321 professional singers to gain insights on the lived experiences of pregnant singers. This investigation explored what people were told about the effects of pregnancy on the voice in comparison to what they actually experienced. Results show that about half of the respondents' experience matched what they were told for respiration. For phonation and vocal quality less than 25% respondent's experience matched what they were told. In addition, most of the information respondents received came from friends, colleagues, and teachers compared to medical professionals suggesting a need for more interdisciplinary education to best prepare vocalists who are contemplating becoming pregnant.

Coastal social-ecological systems are vulnerable to climate change with impacts distributed unequally amongst human communities. Vulnerability assessments, an increasingly popular methodology for understanding variability in vulnerability and its components, often fail to include or recognize the perceptions of individuals in the focal system. Perceptions of climate vulnerability are influenced by experiences, social networks, and cognitive biases, and often differ from vulnerability as measured by subject experts. Because perceptions influence human behavior, including if and how people take adaptive action, a failure to recognize perceptions can lead to ineffective adaptation plans and an incomplete understanding of system vulnerability. Here, as part of a novel, multi-method effort to evaluate vulnerability to climate change in the California Current social-ecological system, we survey fishers from Washington, Oregon, and California to understand their perceived vulnerability and investigate what factors drive variability in their views. We find that while there is a connection between some factors known to influence vulnerability of fishers, including vessel size and the diversity of fishing portfolios, the most significant predictor of higher perceived vulnerability was environmental worldview, specifically a belief that climate change is occurring. Motivation to adapt is also influenced by the sentiment that the impacts of climate change are more urgent and consequential than other problems; thus, we also evaluate how concern levels for environmental issues compare to other challenges that may affect fishing success and wellbeing. While just under half think that they will be personally harmed by climate change, generally the fishers were more concerned about issues like costs and regulations than they were about environmental impacts. This assessment of perceptions highlights the importance of communication and addressing cognitive barriers to adaptation in the effort to develop climate resilient fisheries and fishing communities in the United States.

The immense challenges associated with realizing ocean and coastal sustainability require highly skilled interdisciplinary marine scientists. However, the barriers experienced by early career researchers (ECRs) seeking to address these challenges, and the support required to overcome those barriers, are not well understood. This study examines the perspectives of ECRs on opportunities to build interdisciplinary research capacity in marine science. We engaged 23 current and former graduate students and postdoctoral fellows in a policy Delphi method with three rounds of surveying that included semi-structured questionnaires and q-methodology. We identified the following five barriers that limit ECRs’ capacity for interdisciplinary research: (i) demanding workloads; (ii) stress linked to funding, publishing, and employment uncertainty; (iii) limited support for balancing personal and professional commitments; (iv) ineffective supervisory support; and (v) the steep learning curve associated with interdisciplinary research. Our analysis highlights three main types of responses to these barriers adopted by ECRs, including “taking on too much”, “coping effectively”, and “maintaining material wellbeing at any cost”. To overcome these barriers, we propose the following three institutional actions to build early career interdisciplinary researcher capacity: formalize mentorship, create interdisciplinary research groups, and mainstream mental health support.

Introduction Cognitive behavior therapy for insomnia (CBT-I), a first-line therapy for patients with chronic insomnia disorder (ChID), is underutilized due to reduced access to trained providers and other barriers. We developed an interactive care plan (ICP) combining individual aspects of CBT-I. This ICP, which integrates with the electronic health record (EHR), is designed to deliver personalized and scalable CBT-I to patients with ChID. We report data from initial implementation and evaluation of a ChID ICP deployed at a tertiary sleep medicine clinic. Methods The ICP was developed following patient and provider interviews and focus groups. Patients diagnosed with ChID were offered enrollment and engaged in the ICP through an app. The ICP has embedded logic that may escalate care or offer an exit from the program, depending upon the patient’s response to questions. Key variables ascertained from the patient included sleep efficiency (SE), sleep timing and the Insomnia Severity Index (ISI), and how satisfied they were with their progress (Likert scale). We also measured In Basket messaging related to use of the ICP. Results A total of 222 patients [57% female, age=56.4±15.9 years (average ±SD), 92.7% white] were enrolled in the initial 120 days of ICP implementation. Most referrals were initiated by physicians or advanced practitioners (77.9%). ISI at initiation was 15±5.18 and SE was 74.55±16.65%. Patients spent 35.9±26.25 days engaging with the ICP. The ISI score at 28 days was 12.89±4.98 and SE was 78.9±13.4% with both showing significant improvement from baseline (p=0.013; p=0.002; respectively). Self-rated satisfaction with progress did not significantly correlate with actual improvement in ISI or SE (p>0.05). The ICP generated 3.89±2.3 In Basket messages per patient. Conclusion Patients who actively engaged with the ICP showed significant improvements in insomnia severity and sleep efficiency. While a majority of the patients were neutral towards the ICP and only a small minority expressed dissatisfaction, these data indicate that the ICP will have clinical utility in busy sleep medicine practices with reduced access to behavioral sleep specialists. Support (If Any)

Functional genomics approaches can overcome limitations—such as the lack of identification of robust targets and poor clinical efficacy—that hamper cancer drug development. Here we performed genome-scale CRISPR–Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes. We verified one of our most promising dependencies, the Werner syndrome ATP-dependent helicase, as a synthetic lethal target in tumours from multiple cancer types with microsatellite instability. Our analysis provides a resource of cancer dependencies, generates a framework to prioritize cancer drug targets and suggests specific new targets. The principles described in this study can inform the initial stages of drug development by contributing to a new, diverse and more effective portfolio of cancer drug targets. In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

The traditional cultural norm in China is that eldercare should be offered by a son and his family. However, several decades of family planning policies and rapid economic growth have led to low fertility rates, urbanisation, and cultural change, resulting in both reduced household size and the availability of sons. The traditional eldercare system is thus being challenged, especially in urban areas, with an increasing number of daughters supporting their parents, enabled by rising female empowerment, formal economic employment and improved financial capacities. Existing studies examine and compare the amount and types of support provided by sons and daughters, but very little is known about the differential health outcomes of parents experiencing eldercare offered by sons and by daughters.This study investigates the difference in mental health outcomes of parents who receive eldercare from their sons and from their daughters.We analyse waves 2013, 2015, and 2018 of the China Health and Retirement Longitudinal Study, with mental health measured by a 10-item Center for Epidemiological Studies-Depression (CES-D-10) score. We compare the CES-D-10 score between parents with different sources of care - son's family, daughter's family or other - with multivariate statistical analysis.Receiving regular care from a son (or a daughter-in-law) is associated with a lower CES-D score than from a daughter (or a son-in-law). The difference mainly exists amongst those with a stronger son preference and those who are heavily deponent on their children, in particular rural parents, mothers, and those with less wealth.Our study explores the evidence on mental health inequalities among parents with different sources of care, highlighting that lack of son care creates an apparent mental health disadvantage. Lowering older adults' dependency on their children may alleviate this inequality by improving their financial independence. We also suggest the development of a long-term care system and greater facilitation of older adults to take-up supplementary services for family care.

Sustainably managed wild fisheries support food and nutritional security, livelihoods, and cultures (1). Harmful fisheries subsidies—government payments that incentivize overcapacity and lead to overfishing—undermine these benefits yet are increasing globally (2). World Trade Organization (WTO) members have a unique opportunity at their ministerial meeting in November to reach an agreement that eliminates harmful subsidies (3). We—a group of scientists spanning 46 countries and 6 continents—urge the WTO to make this commitment...

Introduction A novel variant in the thrombomodulin (TM) gene, c.1487delC,p.(Pro496Argfs*10), referred to as Pro496Argfs*10, was identified in a family with an unexplained bleeding disorder. The Pro496Argfs*10 variant results in loss of the transmembrane and intracellular segments of TM and is associated with an increase in soluble TM (sTM) in the plasma. The aim of this study was to characterise the effect of elevated sTM on thrombin generation (TG) and fibrinolysis, and to evaluate therapeutic strategies to manage the patients. Methods Plasma samples were obtained from two patients carrying the variant. TG was triggered using 5 pM tissue factor and measured using the Calibrated Automated Thrombogram. A turbidity clot lysis assay was used to monitor fibrinolysis. TM antigen was quantified by ELISA. Results Patients with the Pro496Argfs*10 variant had significantly elevated plasma sTM compared to controls (372.6 vs. 6.0 ng/ml). TG potential was significantly lower in patients but was restored by inhibition of activated protein C (APC) or addition of activated Factor VII (FVIIa) or platelet concentrates. In vitro experiments suggested that activated prothrombin complex concentrates (APCC) posed a risk of thrombosis. The time to 50% lysis was significantly prolonged in patients compared to controls, 69.7 vs. 42.3 min. Clot lysis time was shortened by inhibition of activated thrombin activatable fibrinolysis inhibitor (TAFIa). Conclusions Our data demonstrate that increased sTM enhances APC generation and reduces TG. Simultaneously, the rate of fibrinolysis is delayed due to increased TAFI activation by sTM. Treatment with platelet or FVIIa concentrates may be beneficial to manage this rare bleeding disorder.

The liver synthesises the majority of pro‐ and anti‐ coagulant and fibrinolytic proteins, and during liver dysfunction synthesis of these proteins is reduced. The end point of conventional haemostatic tests, such as the prothrombin time (PT), occurs when only 5% of thrombin generation (TG) has taken place and is not sensitive to the effects of natural anti‐coagulants. The aim of this study was to determine whether TG in the presence of thrombomodulin (TM) provides more useful information about coagulation potential, in comparison to the PT. Analysis was performed on ST Genesia, a novel TG analyser from Diagnostica Stago. TG was measured using STG‐Thromboscreen; a reagent containing an intermediate concentration of human tissue factor (TF) ± rabbit TM to account for anti‐coagulant protein C activity. Platelet‐poor plasma (PPP) samples from the Intensive Care Study of Coagulopathy‐2 (ISOC‐2), which recruited patients admitted to critical care with a prolonged PT (3 seconds above the reference range). Despite a prolonged PT, 48.0 and 60.7% of patients in the liver and non‐liver groups had TG parameters within the normal range. Addition of TM reduced TG by 34.5 % and 41.8 % in the liver and non‐liver groups, respectively. Interestingly, fresh frozen plasma (FFP) transfusion had no impact on TG. Measurement of TG with addition of TM provides a more informative assessment of coagulation capacity and indicates that haemostasis is balanced in patients with liver disease during critical illness, despite conventional tests suggesting that bleeding risk is increased. ESSENTIALS • The end point of conventional haemostatic tests occur when only 5 % of thrombin generation has taken place and are insensitive to natural anti‐coagulants. • Thrombin generation performed on a fully automated analyser in the presence of thrombomodulin may provide a more accurate interpretation of an individual’s coagulation potential. • Patients with liver disease have balanced haemostasis and are not significantly different from those without liver disease. • Fresh frozen plasma transfusion did not alter a patients thrombin generation and may not be necessary for minor procedures.