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Arabic, one of the official languages of the United Nations, is spoken by more than half a billion people around the world and is of increasing importance in today's political and economic spheres. The study of the Arabic language has a long and rich history: earliest grammatical accounts date from the 8th century and include full syntactic, morphological, and phonological analyses of the vernaculars and of Classical Arabic. In recent years the academic study of Arabic has become increasingly sophisticated and broad. This state-of-the-art volume presents the most recent research in Arabic linguistics from a theoretical point of view, including computational linguistics, syntax, semantics, and historical linguistics. It also covers sociolinguistics, applied linguistics, and discourse analysis by looking at issues such as gender, urbanization, and language ideology. Underlying themes include the changing and evolving attitudes of speakers of Arabic and theoretical approaches to linguistic variation in the Middle East.

In this thesis the semantics distinction between stative and non-stative predicates is explored. The hypothesis that statives are predicates of situations, but non-statives are predicates of events is argued for at length. Ramifications of this hypothesis are explored. In the first chapter, the logical and distributional distinction among the traditional Vendlerian aspectual categories are drawn. There is a discussion of the logic of plurals and masses and this is related to the logic of time. Times are modeled as a certain type of mass individual, and temporal quantifiers such as all day are taken to be logically analogous to mass quantifiers such as all of the water. The distinction between events and situations is drawn, and the stative/non-stative distinction is made. In the second chapter, six contexts which distinguish stative and non-stative predicates are examined in detail. These contexts are: the temporal interpretation of sentences in discourse, the interpretation of quantificational adverbs and of time-span adverbials, the interpretation of the past tense and of the present tense, and the interpretation of when-clause modification. Each of these contrasts is shown to follow, more or less directly, from the hypothesized contrast between statives and non-statives. The relationship of adverbials to the interpretations of sentences is considered. Finally, in the last chapter, there is an extended discussion of genericity and habituality. Habituals are argued to be quantificational. This quantificationality accounts for their aspectual stativity. In course of this discussion an account of the distinctions between \"stage-level\" predicates, such as be happy, and \"individual-level\" predicates, such be tall is given. This account rejects the recent proposals of Diesing in favor of a treatment which takes individual-level predicates to be inherently habitual. Semantically, then, the sentence Texans are tall, is taken to have the same representation as a habitual sentence Boys eat beans. This account explains the quantificational variability of bare plural subjects in a natural way.

Background Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term. Over the short-term, we hypothesize that engaging in URT will deplete attentional resources and result in worse cognitive performance in daily life. Over the long-term, we expect that the effects of chronic stress, from repeated exposure to stressors and regular engagement in URT, will be apparent in dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and inflammation. Over time, stress-related physiological dysregulation will result in accelerated cognitive decline. Methods/Design This study utilizes a prospective longitudinal measurement-burst design. A systematic probability sample of participants aged 25 to 65 is recruited from residents of the Bronx, NY. Consenting participants complete a baseline assessment and follow-up waves at 9, 18, and 27 months post-baseline. At each wave, participants complete a 14 day measurement burst of brief surveys and cognitive assessments delivered via study smartphones during daily life. Participants provide saliva samples four times each day for five days during the measurement burst and fasting blood samples at the end of each burst from which cortisol and dehydroepiandrosterone sulfate (DHEAS), circulating inflammatory markers, and stimulated inflammatory responses to lipopolysaccharide in whole blood are determined. Discussion This study takes a multi-pronged approach to assessing stress (i.e., early adversity, chronic strains, major events, daily hassles), psychological mediators (e.g., URT), biological mechanisms (i.e., HPA function, inflammation) and outcomes across different time-scales (i.e., momentary cognitive performance, cognitive decline across years). The systematic probability sample is locally representative and can be compared with national norms on key markers of health and well-being. The findings will improve our understanding of how environmental, psychological, and physiological stress-related influences accumulate to affect cognitive health and identify potential targets (e.g., URT, inflammation) for prevention and intervention promoting cognitive health.

Peter Gregersen and colleagues identify a regulatory variant in CSK , coding for an intracellular kinase that physically interacts with Lyp ( PTPN22 ), associated with systemic lupus erythematosus (SLE). Their work suggests that the Lyp-Csk complex influences susceptibility to SLE through regulation of B-cell signaling, maturation and activation. The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22 ) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its location to the intronic polymorphism rs34933034 (odds ratio (OR) = 1.32; P = 1.04 × 10 −9 ). The risk allele at this SNP is associated with increased CSK expression and augments inhibitory phosphorylation of Lyn. In carriers of the risk allele, there is increased B-cell receptor (BCR)-mediated activation of mature B cells, as well as higher concentrations of plasma immunoglobulin M (IgM), relative to individuals with the non-risk haplotype. Moreover, the fraction of transitional B cells is doubled in the cord blood of carriers of the risk allele, due to an expansion of late transitional cells in a stage targeted by selection mechanisms. This suggests that the Lyp-Csk complex increases susceptibility to lupus at multiple maturation and activation points in B cells.

Background Prospective memory (PM; i.e., memory for future actions or events) lapses, such as forgetting to attend an appointment or take medication on time, may be one of the earliest indicators of mild cognitive impairment (MCI) and Alzheimer's Disease and related dementias (ADRD). Yet, limited work has examined links between PM and biomarkers of ADRD such as neurodegenerative biomarkers. Determining such associations may be crucial in early identification of MCI and ADRD risk. The present work addressed this gap by examining self‐reported PM lapses and blood‐based levels of β‐amyloid and tau biomarkers among older adults. Method Older adults (N = 275, Mage=77.02, 68% female, non‐Hispanic White) enrolled in the Einstein Aging Study completed a two‐week protocol, that included blood draws for biomarker assays of β‐amyloid (Aβ40, Aβ42, Aβ42:Aβ40) and phosphorylated tau (pTau181). Participants reported PM lapses at the end of each day of the two‐week period via study‐provided smartphones. Independent regression analyses examined links between neurodegenerative biomarkers and PM lapses (daily reports averaged across the two weeks) within the full sample and stratified by gender. Covariates included age and educational attainment. Result Higher levels of pTau181 were associated with reporting more PM lapses on average across the two weeks (b = 0.01, p = .005). When examined within gender, this effect appeared to be driven by women: higher levels of pTau181 were associated with reporting more PM lapses among women (n = 186, b = 0.02, p < .001) but not men (n = 89, b = 0.00, p = .678). No significant relationships emerged with β‐amyloid (ps>.123). Conclusion The present findings indicate that in older adults, PM lapses are related to elevated levels of pTau181 in women by not men. This finding is noteworthy, as markers of pTau181 are detectable in blood in preclinical Alzheimer's disease and increases correlate with risk of disease progression. As such, women experiencing more frequent PM forgetting and elevated levels of pTau181 may be at risk for future pathology. However, longitudinal research is needed to determine whether this relationship persists across time and its association with objective cognitive decline. Continued research in this area may inform early risk detection for MCI and ADRD.

Inappropriate health care leads to negative patient experiences, poor health outcomes and inefficient use of resources. We aimed to conduct a systematic review of inappropriately used clinical practices in Canada. We searched multiple bibliometric databases and grey literature to identify inappropriately used clinical practices in Canada between 2007 and 2021. Two team members independently screened citations, extracted data and assessed methodological quality. Findings were synthesized in 2 categories: diagnostics and therapeutics. We reported ranges of proportions of inappropriate use for all practices. Medians and interquartile ranges (IQRs), based on the percentage of patients not receiving recommended practices (underuse) or receiving practices not recommended (overuse), were calculated. All statistics are at the study summary level. We included 174 studies, representing 228 clinical practices and 28 900 762 patients. The median proportion of inappropriate care, as assessed in the studies, was 30.0% (IQR 12.0%–56.6%). Underuse (median 43.9%, IQR 23.8%–66.3%) was more frequent than overuse (median 13.6%, IQR 3.2%–30.7%). The most frequently investigated diagnostics were glycated hemoglobin (underused, range 18.0%–85.7%, n = 9) and thyroid-stimulating hormone (overused, range 3.0%–35.1%, n = 5). The most frequently investigated therapeutics were statin medications (underused, range 18.5%–71.0%, n = 6) and potentially inappropriate medications (overused, range 13.5%–97.3%, n = 9). We have provided a summary of inappropriately used clinical practices in Canadian health care systems. Our findings can be used to support health care professionals and quality agencies to improve patient care and safety in Canada.

Background Inflammation is a risk factor for cognitive decline, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). While past research in laboratory settings suggests that inflammation relates to cognitive decline and MCI status, more research is needed to examine such associations in everyday life. The present work addressed this gap by examining MCI and gender stratified links between circulating inflammatory biomarkers and self‐reported prospective memory (PM; i.e., memory for future events) and retrospective memory (RM; i.e., memory for past events/information) lapses measured at the end of each day via daily dairies. Method Older adults (n=270, Mage=76.97, 68% female) enrolled in the Einstein Aging Study were classified with or without MCI using Jak/Bondi criteria. Participants completed a two‐week protocol, including two blood draws (at the start and end of the protocol) from which circulating (basal) cytokines were quantified (interleukin [IL]‐1b, IL‐4, IL‐6, IL‐8, IL‐10, tumor necrosis factor‐alpha [TNF‐α]). Each night, participants completed reports of PM and RM lapses that had occurred that day via smartphones. Correlations between inflammatory markers (averaged across the two draws) and memory lapses stratified by MCI status and gender were estimated. Results Among those with MCI, men (n=23) exhibited higher levels of circulating IL‐10 in association with more frequent PM lapses (r=.47, p=.025) and women (n=55), exhibited higher circulating IL‐6 in association with more frequent RM lapses (r=.28, p=.035). Among those without MCI higher levels of IL‐8 correlated with more frequent PM lapses only in men (n=64; r=.39, p=.002). Findings held when controlling for BMI, age, and education. Conclusion The present research suggests that MCI‐ and gender‐dependent links between inflammation and everyday memory lapses may be restricted to certain inflammatory cytokines. IL‐10 and IL‐6 may play a role in MCI‐related daily forgetting among men and women, respectively. However, these findings should be replicated within a larger sample of individuals experiencing MCI. Additionally, longitudinal research is needed to determine whether IL‐8 is indicative of early cognitive decline prior to MCI in men. Longitudinal examinations will better elucidate the links between inflammation, memory lapses, and MCI, and might ultimately inform early risk detection for MCI and AD.

Observations of an event (several energetic eruptions leading to a terminal explosion that is surprisingly hydrogen-rich) with the spectrum of a supernova do not match with other observations of supernovae. A very unusual supernova Thousands of 'core-collapse' supernovae have been observed over the past 15 years, with common observational elements such as hydrogen absorption lines that slow over time and a single light-curve peak or luminosity that plateaus for around 100 days before declining. Iair Arcavi and colleagues report observations of the supernova iPTF14hls, which does not display the usual elements. Its light curve has multiple peaks and extends over 600 days. They conclude that the properties could be explained by ejection of several tens of solar masses of gas a few hundred days before the explosion, but there is no viable explanation for how this occurred. Although multiple pre-supernova eruptions are predicted by the pulsational pair instability, that model is inconsistent with the energetics involved here and the continued presence of hydrogen absorption lines with no decrease in velocity. Every supernova so far observed has been considered to be the terminal explosion of a star. Moreover, all supernovae with absorption lines in their spectra show those lines decreasing in velocity over time, as the ejecta expand and thin, revealing slower-moving material that was previously hidden. In addition, every supernova that exhibits the absorption lines of hydrogen has one main light-curve peak, or a plateau in luminosity, lasting approximately 100 days before declining 1 . Here we report observations of iPTF14hls, an event that has spectra identical to a hydrogen-rich core-collapse supernova, but characteristics that differ extensively from those of known supernovae. The light curve has at least five peaks and remains bright for more than 600 days; the absorption lines show little to no decrease in velocity; and the radius of the line-forming region is more than an order of magnitude bigger than the radius of the photosphere derived from the continuum emission. These characteristics are consistent with a shell of several tens of solar masses ejected by the progenitor star at supernova-level energies a few hundred days before a terminal explosion. Another possible eruption was recorded at the same position in 1954. Multiple energetic pre-supernova eruptions are expected to occur in stars of 95 to 130 solar masses, which experience the pulsational pair instability 2 , 3 , 4 , 5 . That model, however, does not account for the continued presence of hydrogen, or the energetics observed here. Another mechanism for the violent ejection of mass in massive stars may be required.

Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.