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This study examines the fluting of two well‐known Late Pleistocene fluted point types in North America: Clovis and Folsom. Using scaling analyses, we assess the changing relationship between flute length and point length in a large sample of each type. Researchers use scaling to investigate the physical constraints of an object and determine how its dimensions change with size. We compare the strength and consistency of the scaling relationships between the older Clovis and the younger Folsom with the aim of shedding light on scaling differences, if any, over their temporal span. Our results show that there is a significant difference in the relationship of fluting length to point length between these types. In Folsom point manufacture, flute length increases nearly twice as fast with increasing point length than in Clovis. Importantly, the scaling of flute length to point length relationship is isometric (linear) in the Folsom sample, whereas it is allometric (sublinear) in the Clovis sample. In other words, Folsom flintknappers maintained a constant ratio of flute length to point length. Clovis flintknappers were less concerned about maintaining this ratio. We attribute this difference to a potentially increasing, or changing, functional role of fluting in Folsom. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are increasingly prevalent in the aging population, yet no disease‐modifying treatments are currently available. Increasing the expression of the cold‐shock protein RBM3 through therapeutic hypothermia is remarkably neuroprotective. However, systemic cooling poses a health risk, strongly limiting its clinical application. Selective upregulation of RBM3 at normothermia thus holds immense therapeutic potential. Here we identify a poison exon within the RBM3 gene that is solely responsible for its cold‐induced expression. Genetic removal or antisense oligonucleotide (ASO)‐mediated manipulation of this exon yields high RBM3 levels independent of cooling. Notably, a single administration of ASO to exclude the poison exon, using FDA‐approved chemistry, results in long‐lasting increased RBM3 expression in mouse brains. In prion‐diseased mice, this treatment leads to remarkable neuroprotection, with prevention of neuronal loss and spongiosis despite high levels of disease‐associated prion protein. Our promising results in mice support the possibility that RBM3‐inducing ASOs might also deliver neuroprotection in humans in conditions ranging from acute brain injury to Alzheimer's disease. Synopsis: Alternative splicing coupled to nonsense‐mediated decay is revealed to control cold‐induced expression of the neuroprotective protein RBM3. Inducing RBM3 by modulating its alternative splicing through ASOs at normothermia is neuroprotective in vivo and has great therapeutic potential. Cold‐induced expression of the neuroprotective protein RBM3 is controlled through alternative splicing coupled to nonsense‐mediated decay.Mapping cis‐regulatory elements in the RBM3 poison exon reveals an evolutionarily conserved exonic splicing enhancer (ESE).Targeting the ESE using ASOs with FDA‐approved chemistry leads to a long‐lasting increase of RBM3 at normothermia.An RBM3‐inducing ASO is strongly neuroprotective in a mouse model for prion disease and holds great promise as a therapeutic strategy in other neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

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Many institutions have found the strength to name racism and seek space for curriculum and other systemic changes. We argue this is happening against a backdrop of curriculum, regulatory and policy changes in education, and particularly initial teacher education and training (ITE/T), which are de‐racialised. We propose that a 'pocket of possibility' lies within such divergences, and present research leading to the creation of an anti‐racism framework for ITE/T to support action against this emergent landscape. The paper documents each aspect of the research and snapshots of the findings of a global literature review of anti‐racism in initial teacher education, which demonstrated the need for an embedded approach to anti‐racism, informed by critical understandings of whiteness and racism. We share some of the complexities, obstacles, and effective anti‐racism practices revealed in the review. The findings of the review led to the creation and analysis of a survey for ITE/T providers in England, which provided encouraging evidence of useful practice alongside needs of the profession. We conclude with a statement of intent and hope to maximise of the minimum entitlement of the Core Content Framework (CCF) by a purposeful undoing of the perpetual de‐racialisation of education. [ABSTRACT FROM AUTHOR]

The questions we ask and how we ask them will make a difference in how successful we are in meetings, in collaborations and in our careers as statisticians and data scientists. What makes a question good and what makes a good question great? Great questions elicit information useful for accomplishing the tasks of a project and strengthen the statistician–domain expert relationship. Great questions have three parts: the question, the answer and the paraphrasing of the answer to create shared understanding. We discuss three strategies for asking great questions: preface questions with statements about the intent behind asking the question; follow the question with behaviours and actions consistent with the prefaced words including actions such as listening, paraphrasing and summarizing; and model a collaborative relationship via the asking of a great question. We describe the methods and results of a study that shows how questions can be assessed, that statisticians can learn to ask great questions and that those who have learned this skill consider it to be valuable for their careers. We provide practical guidelines for learning how to ask great questions so that statisticians can improve their collaboration skills and thus increase their impact to help address societal challenges. [ABSTRACT FROM AUTHOR]

Background: Diagnoses of both melanoma and nonmelanoma skin cancers are becoming increasingly common among young adults. Interventions in this population are a priority because they do not consistently follow skin cancer prevention recommendations. Objectives: The goal of the current study was to examine college students' perspectives on and experience with receiving a skin cancer prevention intervention that provided personalized skin cancer risk feedback in the form of an ultraviolet (UV) photograph, the results of genetic testing for common skin cancer risk variants, and/or general skin cancer prevention education. Methods: Qualitative interviews were conducted with 38 college students who received a skin cancer prevention intervention. The interview covered students' feelings about their personal skin cancer risk information, the impact of the intervention on their skin cancer risk perceptions, actions or intentions to act with regard to their sun protection practices and feedback for improvement of the intervention content or delivery. Results: Participants reported that different intervention components contributed to increased awareness of their sun protection behaviours, shifts in cognitions about and motivation to implement sun protection strategies and reported changes to their skin cancer prevention strategies. Conclusion: Our findings indicate that college students are interested in and responsive to these types of multicomponent skin cancer preventive interventions. Further, students demonstrate some motivation and intentionality toward changing their skin cancer risk behaviour in the short term. Patient or Public Contribution: Participants involved in this study were members of the public (undergraduate students) who were involved in a skin cancer prevention intervention, then participated in semistructured interviews, which provided the data analysed for this study. [ABSTRACT FROM AUTHOR]

SUMMARY: Tomato has undergone extensive selections during domestication. Recent progress has shown that genomic structural variants (SVs) have contributed to gene expression dynamics during tomato domestication, resulting in changes of important traits. Here, we performed comprehensive analyses of small RNAs (sRNAs) from nine representative tomato accessions. We demonstrate that SVs substantially contribute to the dynamic expression of the three major classes of plant sRNAs: microRNAs (miRNAs), phased secondary short interfering RNAs (phasiRNAs), and 24‐nucleotide heterochromatic siRNAs (hc‐siRNAs). Changes in the abundance of phasiRNAs and 24‐nucleotide hc‐siRNAs likely contribute to the alteration of mRNA gene expression in cis during tomato domestication, particularly for genes associated with biotic and abiotic stress tolerance. We also observe that miRNA expression dynamics are associated with imprecise processing, alternative miRNA‐miRNA* selections, and SVs. SVs mainly affect the expression of less‐conserved miRNAs that do not have established regulatory functions or low abundant members in highly expressed miRNA families. Our data highlight different selection pressures on miRNAs compared to phasiRNAs and 24‐nucleotide hc‐siRNAs. Our findings provide insights into plant sRNA evolution as well as SV‐based gene regulation during crop domestication. Furthermore, our dataset provides a rich resource for mining the sRNA regulatory network in tomato. Significance Statement: The change of epigenetic regulation during crop domestication, particularly with regard to the dynamic expression and function of small RNAs (sRNAs), has rarely been characterized in a systematic manner. Here, we report the comprehensive comparative investigation of sRNA expression dynamics during tomato domestication, which reveals differential selection pressures over distinct classes of sRNAs and structural variants as a driving force for the dynamic expression of sRNAs in the history of tomato breeding. [ABSTRACT FROM AUTHOR]

Successful health outcomes require a positive alliance between health provider and patient, especially for older patients often managing chronic medical conditions. We predicted that age differences between physician and patient could serve as a social category cue that impacts older patients' cooperation. Older adults evaluated a hypothetical physician visit (Study 1, N = 308), a hypothetical physician's web page (Study 2, N = 339) or described their most recent visit to a physician (Study 3, N = 448). Physician treatment (e.g., respect) and visit outcomes (e.g., the physician's ability to recognize and address their symptoms) shaped patients' trust, compliance and willingness to disclose medically relevant information. However, when the physician was much younger than the participant, visit outcomes more strongly predicted their perceptions of physician trustworthiness (Study 1), their willingness to disclose information (Study 3) and their willingness to comply (Studies 1 and 2). When the physician was close to the participants' age, physician treatment shaped participants' willingness to disclose information more strongly (Study 3). Large age differences can prime intergroup differences that make establishing a bond between healthcare provider and patient more challenging. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the risk of contrast‐associated acute kidney injury (CA‐AKI) is low post‐multimodal computed tomography (MMCT) in the evaluation of acute stroke. We provide a complementary study with long‐term renal follow up. A retrospective analysis was performed on all suspected strokes from January 2019 to June 2020 for those who had undergone computed tomography angiography, computed tomography perfusion or both. We identified 776 cases, of which 538 were excluded. The incidence of CA‐AKI was 7.6% (n/N = 18/238; 95% confidence interval = 4.2–11.0). All CA‐AKI cases had renal confounders. No AKI at >30 days was found in 60.5% (n = 144) of all cases studied. The long‐term renal outcome post‐MMCT in stroke evaluation is favourable at >30 days. [ABSTRACT FROM AUTHOR]

Autopsies of patients who have died from COVID‐19 have been crucial in delineating patterns of injury associated with SARS‐CoV‐2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections. We developed a novel autopsy protocol in order to perform postmortem examinations on victims of COVID‐19 and herein describe detailed clinical information, gross findings, and histologic features observed in the first 16 complete COVID‐19 autopsies. We also critically evaluated the role of ancillary studies used to establish a diagnosis of COVID‐19 at autopsy, including immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy (EM). IHC and ISH targeting SARS‐CoV‐2 were comparable in terms of the location and number of infected cells in lung tissue; however, nonspecific staining of bacteria was seen occasionally with IHC. EM was unrevealing in blindly sampled tissues. We then compared the clinical and histologic features present in this series to six archival cases of fatal seasonal influenza and six archival cases of pandemic influenza from the fourth wave of the 'Spanish Flu' in the winter of 1920. In addition to routine histology, the inflammatory infiltrates in the lungs of COVID‐19 and seasonal influenza victims were compared using quantitative IHC. Our results demonstrate that the clinical and histologic features of COVID‐19 are similar to those seen in fatal cases of influenza, and the two diseases tend to overlap histologically. There was no significant difference in the composition of the inflammatory infiltrate in COVID‐19 and influenza at sites of acute lung injury at the time of autopsy. Our study underscores the relatively nonspecific clinical features and pathologic changes shared between severe cases of COVID‐19 and influenza, while also providing important caveats to ancillary methods of viral detection. [ABSTRACT FROM AUTHOR]

Postoperative pancreatic fistula (POPF) is a major source of morbidity following pancreatic resection. Surgically placed drains under suction or gravity are routinely used to help mitigate the complications associated with POPF. Controversy exists as to whether one of these drain management strategies is superior. The objective was to identify and compare the incidence of POPF, adverse events, and resource utilization associated with passive gravity (PG) versus active suction (AS) drainage following pancreatic resection. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from inception to May 18, 2020. Outcomes of interest included POPF, post-pancreatectomy hemorrhage (PPH), surgical site infection (SSI), other major morbidity, and resource utilization. Descriptive qualitative and pooled quantitative meta-analyses were performed. One randomized control trial and five cohort studies involving 10 663 patients were included. Meta-analysis found no difference in the odds of developing POPF between AS and PG (p = 0.78). There were no differences in other endpoints including PPH (p = 0.58), SSI (wound p = 0.21, organ space p = 0.05), major morbidity (p = 0.71), or resource utilization (p = 0.72). The risk of POPF or other adverse outcomes is not impacted by drain management following pancreatic resection. Based on current evidence, a suggestion cannot be made to support the use of one drain over another at this time. There is a trend toward increased intra-abdominal wound infections with AS drains (p = 0.05) that merits further investigation. [ABSTRACT FROM AUTHOR]

Introduction/Aims: We studied a patient with a congenital myasthenic syndrome (CMS) caused by a dominant mutation in the synaptotagmin 2 gene (SYT2) and compared the clinical features of this patient with those of a previously described patient with a recessive mutation in the same gene. Methods: We performed electrodiagnostic (EDX) studies, genetic studies, muscle biopsy, microelectrode recordings and electron microscopy (EM). Results: Both patients presented with muscle weakness and bulbar deficits, which were worse in the recessive form. EDX studies showed presynaptic failure, which was more prominent in the recessive form. Microelectrode studies in the dominant form showed a marked reduction of the quantal content, which increased linearly with higher frequencies of nerve stimulation. The MEPP frequencies were normal at rest but increased markedly with higher frequencies of nerve stimulation. The EM demonstrated overdeveloped postsynaptic folding, and abundant endosomes, multivesicular bodies and degenerative lamellar bodies inside small nerve terminals. Discussion: The recessive form of CMS caused by a SYT2 mutation showed far more severe clinical manifestations than the dominant form. The pathogenesis of the dominant form likely involves a dominant‐negative effect due to disruption of the dual function of synaptotagmin as a Ca2+‐sensor and modulator of synaptic vesicle exocytosis. [ABSTRACT FROM AUTHOR]

Assessment in counseling is strengthened when research exists to demonstrate the psychometric strength of scores from a particular instrument across samples. This study presents a psychometric synthesis of data across 52 publications that met criteria and reported use of the Parent‐Child Relationship Inventory (PCRI; Gerard, 1994) across disciplines and in numerous contexts. Results revealed low score reliability, with aggregated alphas of.63 to.83 and test‐retest coefficients of.62 to.79 over a 1‐year retest period across subscales and total score. There was little evidence of score validity, including no exploratory or confirmatory factor analytic studies, or evidence of diagnostic validity. Cautions for use of the PCRI and implications for professional counselors and researchers are discussed. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has provided an opportunity to rethink the way the majority of patient consultations are conducted, with a move from face‐to‐face visits to remote consultations. This article, which is applicable to all primary care clinicians undertaking medication review, outlines the main principles of optimising remote consultations, with a focus on older people living with frailty during COVID‐19. [ABSTRACT FROM AUTHOR]

Water service providers are being urged to incorporate customer preferences into their investment plans with the relative merits of different elicitation techniques being exposed to greater scrutiny. Though elicitation can be undertaken with a range of methods, there is little understanding of their comparative performance in terms of being able to generate consistent or commensurable outcomes. This study reports an evaluation of both intra and inter method consistency for three preference elicitation methods. Spearman's rank correlation coefficient is used to measure consistency within and between elicitation methods and session transcripts provide additional evidence to support interpretation of the ranking process. Findings exposed low intramethod variation but significant variation in some intermethod comparisons. Discussion focuses on the internal dynamics of each method with conclusions calling for a wider range of methods to be studied so as to improve practitioner confidence in the use of these tools. [ABSTRACT FROM AUTHOR]

Dual‐process theories contend that interplay between higher‐order (i.e., regulatory) and lower‐order (i.e., reactive) systems influences the development of attention in early childhood. We therefore investigated interactions between an aspect of children's top‐down self‐regulation (i.e., effortful control; EC) and positive reactivity (indexed by observed positive affectivity; PA) and negative reactivity (indicated by cortisol stress reactivity and observed fear) in predicting children's early attention problems. We found that observed EC at the age of three predicted lower attention problems 2 years later, controlling for attention problems at baseline. Importantly, the predictive effect of EC was more pronounced for children higher in cortisol stress reactivity at the age of three; this pattern was not found for observed PA or fear. Findings align with dual‐process developmental theories that emphasize the dynamics between regulatory and reactive processes in shaping child development. Our study provides the first evidence supporting dual‐process interactions in the domain of attention problems and has implications for identifying early risk markers and informing early prevention programs for children at greater risk for attention problems. [ABSTRACT FROM AUTHOR]

Colleges and universities are a unique context in which students encounter similar aged peers from a wide range of economic backgrounds. As emerging adults coping with major life transitions, students may be especially sensitive to upward contrasts with other students who have advantages that they feel they deserve (personal relative deprivation or PRD). We surveyed a population of university students when they were second‐ and third‐year students (N = 309), and 2 years later, when they were fourth‐ and fifth‐year students (N = 400). Increased PRD predicted increased anxiety and depression—even after accounting for students' access to social support, the degree to which they identified with the university, and their gender, family income, ethnic background, and whether the student was a first‐generation college student. For a third separate sample of students who completed both surveys (N = 168), PRD predicted students' mental health two years later even after accounting for their earlier anxiety and depression. In all three samples, PRD mediated the relationship between self‐reported family income and mental health. These data indicate that universities and colleges should consider a broad range of interventions and policies that can mitigate the impact of upward social contrasts. [ABSTRACT FROM AUTHOR]

Background: Multiple changes are made to older patients' medicines during hospital admission, which can sometimes cause confusion and anxiety. This results in problems with post‐discharge medicines management, for example medicines taken incorrectly, which can lead to harm, hospital readmission and reduced quality of life. Aim: To explore the experiences of older patients and their family carers as they enacted post‐discharge medicines management. Design: Semi‐structured interviews took place in participants' homes, approximately two weeks after hospital discharge. Data analysis used the Framework method. Setting and participants: Recruitment took place during admission to one of two large teaching hospitals in North England. Twenty‐seven participants aged 75 plus who lived with long‐term conditions and polypharmacy, and nine family carers, were interviewed. Findings: Three core themes emerged: impact of the transition, safety strategies and medicines management role. Conversations between participants and health‐care professionals about medicines changes often lacked detail, which disrupted some participants' knowledge and medicines management capabilities. Participants used multiple strategies to support post‐discharge medicines management, such as creating administration checklists, seeking advice or supporting primary care through prompts to ensure medicines were supplied on time. The level to which they engaged with these activities varied. Discussion and conclusion: Participants experienced gaps in their post‐discharge medicines management, which they had to bridge through implementing their own strategies or by enlisting support from others. Areas for improvement were identified, mainly through better communication about medicines changes and wider involvement of patients and family carers in their medicines‐related care during the hospital‐to‐home transition. [ABSTRACT FROM AUTHOR]

Patterns of articles published in the Journal of Addictions & Offender Counseling from 1998 to 2017 were reviewed in this metastudy. Author and article characteristics for 172 articles are described and analyzed for trends over time. [ABSTRACT FROM AUTHOR]

When organizational authorities or representatives discriminate, it not only impacts the discrimination target; it also affects those who witness it. In this article, we argue that discrimination within workplace and educational contexts implicates the larger organization in which it occurs in two ways. First, it communicates to targets the extent to which the representatives of an organization respect their group. Second, discrimination implicates the morality of the larger group or organization in which it occurs. This second threat to the organization's morality affects all observers, even those who do not share a social category with the target. We argue that both forms of threat can decrease organization identification, well‐being, and increase withdrawal. For all observers, whether one is a member of the targeted group or not, to witness an organizational authority clearly discriminate against another organizational member is distressing and leads to withdrawal. We offer recommendations for policy and decision‐making procedures aimed at (1) adopting organizational decision‐making structures that minimize the opportunity for personal acts of bias (to prevent discrimination before it occurs), and (2) offering those who witness (or experience) discrimination clear avenues for addressing it (to minimize its destructive consequences). If organization members, especially organizational authorities, confront discrimination, it offsets the negative consequences of a single organizational representative's biased behavior. [ABSTRACT FROM AUTHOR]

Effortful control (EC) has important implications for children's development. While both child sex and parenting are related to child EC, and while a literature shows early sex differences in children's responses to care, interactions between care and child sex in predicting EC are not well understood. We therefore examined associations between child sex and early caregiving as predictors of children's development of a specific aspect of EC, inhibitory control (IC). A community sample of 406 three‐year‐old children and their caregivers completed behavioural tasks and observational measures of parenting and IC, and children were re‐assessed for IC at age 5. Results showed that early care influenced change in IC over time, although caregiving was a more important influence on boys' IC than girls; specifically, differences in boys' and girls' IC at age 5 were modest when parenting was positive. The implications of a better understanding of sex differences in associations between parenting and the development of IC in early childhood are discussed. Statement of contribution What is already known on this subject? While sex differences in reactivity to early care in the development of externalizing symptoms have been explored, very little is known about such differences in children's early‐emerging effortful control. What does this study add? Using a longitudinal design and independent, laboratory methods of assessing study constructs, we provide new information showing that early care appears to differentially influence boys' development of inhibitory control, a key aspect of effortful control, in early childhood. [ABSTRACT FROM AUTHOR]

Hippocampal long-term potentiation (LTP) is a cellular memory mechanism. For LTP to endure, new protein synthesis is required immediately after induction and some of these proteins must be delivered to specific, presumably potentiated, synapses. Local synthesis in dendrites could rapidly provide new proteins to synapses, but the spatial distribution of translation following induction of LTP is not known. Here, we quantified polyribosomes, the sites of local protein synthesis, in CA1 stratum radiatum dendrites and spines from postnatal day 15 rats. Hippocampal slices were rapidly fixed at 5, 30, or 120 min after LTP induction by theta-burst stimulation (TBS). Dendrites were reconstructed through serial section electron microscopy from comparable regions near the TBS or control electrodes in the same slice, and in unstimulated hippocampus that was perfusion-fixed in vivo. At 5 min after induction of LTP, polyribosomes were elevated in dendritic shafts and spines, especially near spine bases and in spine heads. At 30 min, polyribosomes remained elevated only in spine bases. At 120 min, both spine bases and spine necks had elevated polyribosomes. Polyribosomes accumulated in spines with larger synapses at 5 and 30 min, but not at 120 min. Small spines, meanwhile, proliferated dramatically by 120 min, but these largely lacked polyribosomes. The number of ribosomes per polyribosome is variable and may reflect differences in translation regulation. In dendritic spines, but not shafts, there were fewer ribosomes per polyribosome in the slice conditions relative to in vivo, but this recovered transiently in the 5 min LTP condition. Overall, our data show that LTP induces a rapid, transient upregulation of large polyribosomes in larger spines, and a persistent upregulation of small polyribosomes in the bases and necks of small spines. This is consistent with local translation supporting enlargement of potentiated synapses within minutes of LTP induction. [ABSTRACT FROM AUTHOR]

Dyadic data from 679 committed couples were used to examine associations between commitment, forgiveness, and perceptions of partner's relationship self-regulation (RSR) behaviors-that is effort and strategies that partners exert to maintain the relationship. We found that for both partners, higher self-reports of commitment and forgiveness were associated with higher perceptions of their partner's RSR. For females, higher commitment and forgiveness were associated with higher male perceptions of her RSR, and higher male forgiveness was associated with higher female perceptions of his RSR. These findings demonstrate the importance of marital virtues and relationship work and give credence to the marital competence model of "other-centeredness" by Carroll et al. (2006, Journal of Family Issues, 27(7), 1001). Clinical implications are discussed. [ABSTRACT FROM AUTHOR]

The water footprint concept has been used by agricultural, commercial, and industrial water users to measure and report their water consumption, assess the magnitude of potential environmental impacts arising from this consumption, and identify opportunities for risk mitigation strategies that promote sustainable water use. However, water and wastewater utilities have not studied and documented the application of this concept in the same manner that other industries have. This article summarizes the growing body of information on the water footprint concept and the opportunities for integrating the concept into water utility planning efforts as a broader means of achieving and maintaining sustainable communities. The application of the water footprint concept for capital improvement planning, water resources decision-making, operational benchmarking, and stakeholder communications is discussed, as is how the methodology, developed by the International Organization for Standardization, can be used for a water utility. [ABSTRACT FROM AUTHOR]

The sphingosine-1-phosphate 1 receptor (S1P1R) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R receptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases. This first-in-human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose-escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose-limiting toxicities. The most common ozanimod-related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady-state volume of distribution (73-101 L/kg), moderate oral clearance (204-227 L/h), and an elimination half-life of approximately 17 to 21 hours. Ozanimod produced a robust dose-dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose-dependent negative chronotropic effect was observed following the first dose, with the dose-escalation regimen attenuating the first-dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once-daily regimens under clinical investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT In adult hippocampus, long-term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long-Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta-burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three-dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion-fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS-related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

There is a growing body of qualitative literature describing the lived experiences of people with tic disorders (TDs). The aim of this paper was to conduct a systematic review of this literature, synthesizing the perspectives of individuals on their experiences. Meta-synthesis methodology was utilized to review and draw together findings from 10 articles, from which key concepts were extracted, and over-arching themes generated. Six themes were identified to encompass the experience of TDs, including (1) cultural, semantic issues of the condition; (2) negative experiences in organizations and treatment; (3) the value and negative impact on interpersonal relationships; (4) personal identity in the constant presence of TDs; (5) concerns for the future; and (6) strategies to control and manage the observable presence of tics. Adaptive coping strategies were found to encompass continuous social adaptation, strategies to manage tics and social perceptions, self-acceptance, advocacy, and support from others. The results highlighted the significant role of social and cultural issues related to understanding and stigma, which underpinned many of the lived experiences. Implications for clinical practice in supporting individuals with TDs were also highlighted. [ABSTRACT FROM AUTHOR]

Theorists have long argued that two forms of relative deprivation exist: individual-based relative deprivation (IRD) whereby a person feels deprived relative to other individuals and group-based relative deprivation (GRD) whereby a person feels his/her ingroup is deprived relative to other groups. Combinations of IRD and GRD are therefore assumed to produce four response profiles: (i) high on IRD and GRD (i.e. 'doubly deprived'); (ii) high on IRD, low on GRD; (iii) low on IRD, high on GRD; or (iv) low on IRD and GRD. The existence of these profiles, however, has never been assessed. We address this oversight by using latent profile analysis to identify distinct response patterns to measures of IRD and GRD. Across two studies, we found no support for this typology, nor the oft-assumed doubly deprived profile. Rather, response patterns showed moderate levels of IRD across discrete profiles accompanied by considerable variability in GRD. [ABSTRACT FROM AUTHOR]

Although group-based relative deprivation predicts people's willingness to protest unfair outcomes, perceiving that one's subgroup is respected increases employees' support for organizations. An integration of these perspectives suggests that subgroup respect will dampen the impact of group-based relative deprivation on workers' responses to unfair organizational outcomes. We examined this hypothesis among university faculty ( N = 804) who underwent a system-wide pay cut. As expected, group-based relative deprivation predicted protest intentions. This relationship was, however, muted among those who believed university administrators treated their area of expertise (i.e., their subgroup) with a high (vs. low) level of respect. Moderated mediation analyses confirmed that group-based relative deprivation had a conditional indirect effect on protest intentions via participants' (dis)identification with their university at low to moderate, but not high, levels of subgroup respect. Our finding that satisfying relational needs can attenuate responses to group-based relative deprivation demonstrates the benefits of integrating insights from distinct research traditions. [ABSTRACT FROM AUTHOR]

Relative deprivation (RD) is the product of an upward comparison that indicates that one's disadvantaged situation is undeserved coupled with anger and resentment. RD is associated with reduced psychological and physical health, individual deviance, and collective action, but empirical tests of RD are inconsistent. Closer attention to three central features of the RD experience - comparisons, discrete emotions, and the type of outcome - will improve the predictive value of RD. If social scientists measure RD correctly, they can answer the questions about people's surprising tolerance of large inequities in some contexts and unexpected sensitivity to small inequities in other contexts that first motivated RD research. [ABSTRACT FROM AUTHOR]

Ninety-six male fraternity members (Study 1), 112 female voters (Study 2), and 219 undergraduates (Study 3) read scenarios in which a group representative forgave, retaliated, or left a romantic partner after the partner's sexual infidelity was publically revealed. Observers rated a victim who forgave his or her partner to be as mature as a victim who ended the relationship, but also as weaker and less competent. They rated a victim who forgave to be more mature but almost as weak and incompetent as a victim who retaliated. Symbolic concerns that the victim's behavior violated shared values (all three studies) or damaged the group's power/status (Study 3) mediated the relationship between victim behavior and victim ratings. These data demonstrate how the symbolic concerns that shape observers' judgments of an offender can extend to observers' judgments of the victim. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]