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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
This study reports the clinical outcomes of head and neck adenoid cystic carcinoma treatment over a 20-year period.
The treatment outcome of 51 head and neck adenoid cystic carcinoma patients treated between 1992 and 2013 were analysed. Patients were stratified into radical treatment and disease control groups.
A total of 40 patients underwent surgery and post-operative radiotherapy. The 10-year disease-specific survival rate was 93 per cent. Eleven patients had tumour recurrence: of these, nine were pulmonary metastases. The 11 patients in the disease control group had a median follow up of 21 months (range, 2–172 months); 5 underwent radical radiotherapy with palliative intent.
There was late tumour recurrence in over 25 per cent of patients. Adenoid cystic carcinoma has a high tendency to relapse even after radical excision and adjuvant therapy. However, definitive radiotherapy should still be considered on an individual basis because it may provide local control and prolong patient survival.
In this systematic review, we summarized change in Salmonella prevalence and/or quantity associated with pathogen reduction treatments (washes, sprays, steam) on pork carcasses or skin-on carcass parts in comparative designs (natural or artificial contamination).
In January 2015, CAB Abstracts (1910–2015), SCI and CPCI–Science (1900–2015), Medline® and Medline® In-Process (1946–2015) (OVIDSP), Science.gov, and Safe Pork (1996–2012) were searched with no language or publication type restrictions. Reference lists of 24 review articles were checked. Two independent reviewers screened 4001 titles/abstracts and assessed 122 full-text articles for eligibility. Only English-language records were extracted.
Fourteen studies (5 in commercial abattoirs) were extracted and risk of bias was assessed by two reviewers independently. Risk of bias due to systematic error was moderate; a major source of bias was the potential differential recovery of Salmonella from treated carcasses due to knowledge of the intervention. The most consistently observed association was a positive effect of acid washes on categorical measures of Salmonella; however, this was based on individual results, not a summary effect measure.
There was no strong evidence that any one intervention protocol (acid temperature, acid concentration, water temperature) was clearly superior to others for Salmonella control.
These are exciting times for experimental political science. The community of experimental researchers is growing quickly, and these scholars are applying increasingly sophisticated techniques to the study of an ever-widening range of substantive problems. I'm excited, and feel honored, to have been chosen as the new editor of JEPS during this phase of the field's evolution.
We present a model and a laboratory experiment on the informativeness of
debate, varying both informational and institutional variables. The
informational variable we focus on is a novel factor affecting the extent to
which audience members can learn from exposure to unpersuasive arguments.
The more easily a listener can learn from an argument she finds
unpersuasive, the greater the risk that the speaker will alienate this
listener when she fails to persuade her. We find a strong interaction
between speakers’ responsiveness to that risk and the institutions of
debate. When listeners can learn from unpersuasive arguments, many speakers
are discouraged from attempting persuasion, irrespective of the debate rules
we consider. In contrast, when listeners cannot learn from unpersuasive
arguments, debate rules affect speakers’ willingness to engage in
This study examined recent trends in type-specific HPV infection rates in women referred for HPV typing as part of cervical cancer screening in the United States. HPV analyses were performed from March 2004 to March 2011. Women were aged 21–65 years at testing. The 18 most prevalent HPV types were analysed. Type-specific HPV infection rates were estimated in 3-month blocks. Lowess smoothing was used to examine time trends in infection rates for each HPV type, both combined, and separated by age group (younger women 21–30 years, older women 31–64 years). A total of 220914 women were included in the final analysis. The number of HPV tests performed on the younger age group increased, with the number of HPV infections and multiple type HPV infections decreasing. When separated by HPV type-specific analysis, the majority of HPV infection rates decreased; however, HPV types 61 and 83 increased. When analysing the older age group, there was a marked increase of the number of HPV tests. Overall, the rates of any HPV infection, as well as multiple type infections, were lower compared to the younger age group. The change in type-specific HPV rates in the older age group was minimal, with many rates remaining the same. In this population of women, overall rates of HPV infection decreased, while the number of HPV tests increased. Younger women had a more marked decrease in HPV infection rates, while for older women type-specific HPV infection rates appear consistent.
Most individuals with dementia live in the community, receiving care from family or lay carers. Carers’ wellbeing, and the quality of the care they provide, depends on their resilience in the face of the challenges associated with caring for someone with dementia. However, factors associated with carers’ resilience are not yet fully understood. The aim of this review is to present a narrative synthesis of factors, materials and resources associated with carers’ resilience. Electronic and hand searches identified relevant published literature, which was narratively synthesized. A framework consisting of three inter-related domains of factors influencing carers’ resilience emerged, encompassing: social and cultural factors; properties of the care relationship; and carers’ psychological factors. Holistic assessment based on this framework can help practitioners to identify vulnerable carers and to target help on factors that help to make them vulnerable but that are amenable to change.
Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not.
Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement.
Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13.
These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.
In this chapter, I follow other authors (e.g., Kagel and Roth 1995; McDermott 2002; Camerer 2003; Morton and Williams 2010) in focusing on a few key dimensions of difference between experiments in the economic and psychological traditions.
Section 1 considers the level of stylization typical in economics and psychology experimentation. Although research in the political psychology tradition tends to place an emphasis on the descriptive realism of laboratory scenarios, work in experimental economics tends to proceed within a purposefully abstract, “context free” environment.
Section 2 considers the kinds of incentives offered to subjects by experimentalists from these two schools of thought. Experimental economists generally offer subjects monetary incentives that depend on subjects' choices in the laboratory – and, in game-theoretic experiments, the choices of other subjects as well. In contrast, psychology research tends not to offer inducements that are conditional on subjects' actions, instead giving subjects fixed cash payments or fixed amounts of course credit.
Section 3 considers the use of deception. The psychological school tends to see deception as a useful tool in experimentation, and, at times, a necessary one. In contrast, the economic school by and large considers deception to be taboo.
While information for the medical aspects of disaster surge is increasingly available, there is little guidance for health care facilities on how to manage the psychological aspects of large-scale disasters that might involve a surge of psychological casualties. In addition, no models are available to guide the development of training curricula to address these needs. This article describes 2 conceptual frameworks to guide hospitals and clinics in managing such consequences. One framework was developed to understand the antecedents of psychological effects or “psychological triggers” (restricted movement, limited resources, limited information, trauma exposure, and perceived personal or family risk) that cause the emotional, behavioral, and cognitive reactions following large-scale disasters. Another framework, adapted from the Donabedian quality of care model, was developed to guide appropriate disaster response by health care facilities in addressing the consequences of reactions to psychological triggers. This framework specifies structural components (internal organizational structure and chain of command, resources and infrastructure, and knowledge and skills) that should be in place before an event to minimize consequences. The framework also specifies process components (coordination with external organizations, risk assessment and monitoring, psychological support, and communication and information sharing) to support evidence-informed interventions.
(Disaster Med Public Health Preparedness. 2011;5:73-80)
The empirical literature in comparative politics holds that social cleavages affect the number of candidates or parties when electoral institutions are ‘permissive’, but it lacks a theoretical account of the strategic candidate entry and exit decisions that ultimately determine electoral coalitions in plural societies. This article incorporates citizen-candidate social identities into game-theoretic models of electoral competition under plurality and majority-runoff electoral rules, indicating that social group demographics can affect the equilibrium number of candidates, even in non-permissive systems. Under plurality rule, the relationship between social homogeneity and the effective number of candidates is non-monotonic and, contrary to the prevailing Duvergerian intuition, for some demographic configurations even the effective number of candidates cannot be near two. Empirical patterns in cross-national presidential election results are consistent with the theoretical model.
Governments are charged with monitoring citizens’ compliance with prescribed behavioral standards and punishing noncompliance. Flaws in information available to enforcing agents, however, may lead to subsequent enforcement errors, eroding government authority and undermining incentives for compliance. We explore these concepts in a laboratory experiment. A “monitor” player makes punishment decisions after receiving noisy signals about other players’ choices to contribute to a public good. We find that the possibility of wrongly accusatory signals has a more deleterious effect on contribution levels than the possibility of wrongly exculpatory signals. We trace this across-treatment difference to a “false positives trap”: when members of a largely compliant population are sometimes incorrectly accused, some will be unjustly punished if enforcement power is employed, but non-compliant individuals will escape punishment if that power is abdicated. Either kind of error discourages compliance. An additional treatment demonstrates that the functioning of a given enforcement institution may vary, depending on its origins. We consider implications of our findings for theories of deterrence, fairness, and institutional legitimacy.
The oral cavity is a frequent target of chronic graft versus host disease (cGVHD) with changes observed in the lips, muscles, mucosa, salivary glands, dentition, and also in the facial skin. When severe, oral cGVHD is functionally debilitating; however, even mild involvement can have a significant impact on the conduct of daily activities and overall quality of life (QOL). Early recognition and diagnosis of oral changes, provision of appropriate and effective therapies, and vigilant long-term follow-up are critical to minimize complications and to improve both short- and long-term outcomes.
Oral cGVHD is a frequent and, often, very prominent complication following allogeneic hematopoietic cell transplantation (HCT). Almost 80% of patients diagnosed with cGVHD demonstrate some degree of oral involvement, making this one of the most common clinical manifestations. In fact, the prevalence of oral and skin cGVHD is nearly equivalent, making these the two most commonly affected tissues. Although a number of risk factors for the development of cGVHD have been characterized, none specific for the oral cavity have been identified. Standard GVHD prophylaxis regimens are the only specific measures that can prevent or minimize the risk of developing oral cGVHD.
Although oral findings may be the initial and in some cases only indication of cGVHD development, this is highly variable and oral changes may occur at any point along the course of evolution of cGVHD. Also, oral cGVHD may first present clinically as other areas (e.g., skin) are resolving.
Wild house mice, Mus musculus, were bred (a) at 3 °C (‘Eskimo’) and (b) at 23 °C. Mice of the ninth generation bred at 23°C were transferred to the cold environment. Their young, and Eskimo of the same (tenth) generation, were mated to give the four possible types of pairs: controls; the two reciprocal hybrid pairings; and Eskimo. In the resulting (eleventh) generation there were therefore two hybrid classes, genetically identical but with different parentage. The growth and reproduction of the eleventh generation were studied. At all ages from birth, mice with Eskimo mothers were heavier than those with control mothers. They were also better breeders: (1) they matured earlier; (2) their litters were larger; (3) the mortality of their young in the nest was lower. In one feature there was heterosis: of the four classes, the hybrids with Eskimo mothers produced the largest litters. These and previous findings suggest rapid selection, in the cold, for changes in growth, reproductive physiology and other aspects of metabolism. The cold-adapted mice of a given generation differed from the controls partly as a result of favourable parental effects, which acted in conjunction with genetical differences. It is hypothesized that the ecological versatility of Mus musculus depends partly on the presence, in each population, of alternative genotypes which allow rapid adaptation to new conditions.
Magnetofluorescent hybrid nanoparticles consisting of Au layer, an iron oxide moiety, and fluorescent molecules could provide a promising platform for development of multimodal imaging and therapy approaches in the treatment of cancer. However, the feasibility of this platform has yet to be fully explored. In this study, we synthesized biocompatible dumbbell-like iron-gold hybrid particles that are superparamagnetic, fluorescent and with strong optical absorption. Furthermore, we showed that hybrid nanoparticles can be conjugated to targeting agents allowing for specific targeting of cancer cells.
A theory of deliberation must provide a plausible account both of individuals’ choices to speak or to listen and of how they reinterpret their own views in the aftermath of deliberation. We describe a game-theoretic laboratory experiment in which subjects with diverse interests speak or listen before voting over a common outcome. An important feature of our strategic setting is that introspective agents may, upon hearing an unpersuasive argument, update away from the speaker's preferred position. While subjects are responsive to strategic incentives, they also deviate from Bayesian predictions by “overspeaking” when speech is likelier to alienate than persuade. Subjects thus come closer to the deliberative democratic ideal of a free exchange of arguments than equilibrium predictions suggest. We interpret evidence from subjects’ deliberative choices and policy votes in terms of a cognitive hierarchy among subjects, defined by differing abilities to grasp the strategic implications of different kinds of information.
Attentional difficulties reported in individuals with anorexia nervosa (AN) may be due to preferential processing of disease-salient stimuli at a pre-attentive or at a conscious level or to a general problem in attention. Attentional difficulties may be associated with duration of illness.
Female participants with AN (restricting subtype; n=24) and healthy comparison women (n=24) were randomly allocated to subliminal or supraliminal exposure to visual stimuli (food, neutral and aversive images) while performing the 1-back and 2-back working-memory tasks.
Participants with AN made fewer errors than the healthy comparison group in the subliminal condition but significantly more errors in the supraliminal condition [condition×group interaction, F(1, 44)=6.82, p<0.01]: this was irrespective of stimulus type (food, neutral and aversive) and task (1-back or 2-back). The total number of errors made correlated positively with the duration of the AN for both the 1-back task (rs=0.46, p<0.05) and for the 2-back task (rs=0.53, p<0.01).
Decreased ability to concentrate in the presence of explicit distracters is a feature of AN and is associated with longer duration of illness. This phenomenon could be addressed in psychological interventions.
We consider a classical surplus process modified by the payment of dividends when the insurer's surplus exceeds a threshold. We use a probabilistic argument to obtain general expressions for the expected present value of dividend payments, and show how these expressions can be applied for certain individual claim amount distributions. We then consider the question of maximising the expected present value of dividend payments subject to a constraint on the insurer's ruin probability.
Proliferative enteropathy (PE; ileitis) is a common intestinal disease affecting susceptible pigs raised under various management systems around the world. Major developments in the understanding of PE and its causative agent, Lawsonia intracellularis, have occurred that have led to advances in the detection of this disease and methods to control and prevent it. Diagnostic tools that have improved overall detection and early onset of PE in pigs include various serological and molecular-based assays. Histological tests such as immunohistochemistry continue to be the gold standard in confirming Lawsonia-specific lesions in pigs post mortem. Despite extreme difficulties in isolating L. intracellularis, innovations in the cultivation and the development of pure culture challenge models, have opened doors to better characterization of the pathogenesis of PE through in vivo and in vitro L. intracellularis–host interactions. Advancements in molecular research such as the genetic sequencing of the entire Lawsonia genome have provided ways to identify various immunogens, metabolic pathways and methods for understanding the epidemiology of this organism. The determinations of immunological responsiveness in pigs to virulent and attenuated isolates of L. intracellularis and identification of various immunogens have led to progress in vaccine development.
Two new solubility-limiting phases relevant to nuclear waste disposal are reported, namely CeSiO4 and Ca2Ce8(SiO4)O2, produced by hydrothermal synthesis at 180 °C. X-ray diffraction data are presented for both compounds. Rietveld refinement was performed for each of these phases. CeSiO4 was confirmed to be a zircon structure type, with space group I41/amd, unit cell type="bold">abold=6.9564(3), type="bold">cbold=6.1953(4) Å. Bond lengths for SiO4 are in excellent agreement with published values; Ce4+ is coordinated to eight oxygen atoms with four regular and four short bonds. Ca2Ce8(SiO4)O2 was shown to have an apatite structure, with space group P63/m and unit cell type="bold">abold=9.4343(3), type="bold">cbold=6.8885(4) Å. The unit cell and bond lengths were found to be slightly smaller than would be expected from other lanthanide-containing analogs; possible reasons for this are discussed.