RITUAL, TIME, AND ENTERNITY

It is argued here that the construction of time and eternity are among ritual's entailments. In dividing continuous duration into distinct periods ritual distinguishes two temporal conditions: (1) that prevailing in mundane periods and (2) that prevailing during the intervals between them. Differences in the frequency, length, and relationship among the rituals constituting different liturgical orders are considered, as are differences between mundane periods and ritual's intervals with respect to social relations, cognitive modes, meaningfulness, and typical interactive frequencies. Periods, it is observed, relate to intervals as everchanging to never-changing, and close relationships of never changing to eternity, eternity to sanctity, and sanctity to truth are proposed. In the argument that ritual's “times out of time” really are outside mundane time, similarities to the operations of digital computers and Herbert Simon's discussion of interaction frequencies in the organization of matter are noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72989/1/j.1467-9744.1992.tb00996.x.pd

Dementia Caregiver Burden: A Research Update and Critical Analysis

Purpose of Review: This article provides an updated review of the determinants of caregiver burden and depression, with a focus on care demands and especially the differential effects of various neuropsychiatric symptoms or symptom clusters. Moreover, studies on caregivers for frontotemporal and Lewy body dementias were referred to in order to identify differences and similarities with the mainstream literature based largely on Alzheimer caregivers. Recent Findings: As a group, neuropsychiatric symptoms are most predictive of caregiver burden and depression regardless of dementia diagnosis, but the effects appear to be driven primarily by disruptive behaviors (e.g., agitation, aggression, disinhibition), followed by delusions and mood disturbance. Disruptive behaviors are more disturbing partly because of the adverse impact on the emotional connection between the caregiver and the care-recipient and partly because they exacerbate difficulties in other domains (e.g., caring for activities of daily living). In behavioral variant frontotemporal dementia, not only are these disruptive behaviors more prominent but they are also more disturbing due to the care-recipient’s insensitivity to others’ feelings. In Lewy body dementia, visual hallucinations also appear to be distressing. Summary: The disturbing nature of disruptive behaviors cuts across dementia conditions, but the roles played by symptoms that are unique or particularly serious in a certain condition need to be explored further

Do electronic health records affect the patient-psychiatrist relationship? A before & after study of psychiatric outpatients

<p>Abstract</p> <p>Background</p> <p>A growing body of literature shows that patients accept the use of computers in clinical care. Nonetheless, studies have shown that computers unequivocally change both verbal and non-verbal communication style and increase patients' concerns about the privacy of their records. We found no studies which evaluated the use of Electronic Health Records (EHRs) specifically on psychiatric patient satisfaction, nor any that took place exclusively in a psychiatric treatment setting. Due to the special reliance on communication for psychiatric diagnosis and evaluation, and the emphasis on confidentiality of psychiatric records, the results of previous studies may not apply equally to psychiatric patients.</p> <p>Method</p> <p>We examined the association between EHR use and changes to the patient-psychiatrist relationship. A patient satisfaction survey was administered to psychiatric patient volunteers prior to and following implementation of an EHR. All subjects were adult outpatients with chronic mental illness.</p> <p>Results</p> <p>Survey responses were grouped into categories of "Overall," "Technical," "Interpersonal," "Communication & Education,," "Time," "Confidentiality," "Anxiety," and "Computer Use." Multiple, unpaired, two-tailed t-tests comparing pre- and post-implementation groups showed no significant differences (at the 0.05 level) to any questionnaire category for all subjects combined or when subjects were stratified by primary diagnosis category.</p> <p>Conclusions</p> <p>While many barriers to the adoption of electronic health records do exist, concerns about disruption to the patient-psychiatrist relationship need not be a prominent focus. Attention to communication style, interpersonal manner, and computer proficiency may help maintain the quality of the patient-psychiatrist relationship following EHR implementation.</p

Complete sequence of the 22q11.2 allele in 1,053 subjects with 22q11.2 deletion syndrome reveals modifiers of conotruncal heart defects

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p &lt; 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21&nbsp;× 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Análise crítica da aplicação do custeio-meta no desenvolvimento de empreendimentos de habitação de interesse social

O custeio-meta é uma abordagem amplamente aplicada na manufatura e representa uma inovação no processo de desenvolvimento de produtos, em que o custo, a qualidade e a funcionalidade não são conseqüências do processo de projeto, mas parâmetros de entrada. Este artigo investiga a aplicabilidade da abordagem custeio-meta no desenvolvimento de empreendimentos habitacionais de interesse social (EHIS). Tais empreendimentos possuem muitas peculiaridades em relação a produtos da manufatura, não havendo evidências de que esta abordagem seja adequada ao desenvolvimento de EHIS, nem mesmo de produtos da construção civil em geral. Este artigo se propõe a investigar como e por que algumas características dos EHIS - a maioria delas comuns também a outros tipos de empreendimentos de construção - influenciam a aplicabilidade do custeio-meta. Estas questões foram analisadas com base na adaptação de conceitos da manufatura para a construção civil e num estudo de caso exploratório conduzido em uma companhia estadual de provisão habitacional. O estudo propõe adaptar o custeio-meta às condições do contexto de análise, concentrar esforços nas atividades mais vantajosas ou ajustar o contexto de análise de modo a maximizar os seus benefícios e minimizar incertezas

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects

The 22q11.2 deletion syndrome is caused by non‐allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A‐D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation‐SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p = .002), verbal IQ was decreased by 8.17 points (p = .0002) and performance IQ was decreased by 4.03 points (p = .028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B‐D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort

Membaca Jiwa Manusia Seperti Membaca Sebuah Buku

xii + 314 hlm.; 23.5 cm

NPP4 is a procoagulant enzyme on the surface of vascular endothelium

Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that the primary and secondary waves of aggregation and dense granule release are strongly induced by nanomolar NPP4 in a concentration-dependent manner in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors. Collectively, these studies define the biologic and enzymatic basis for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4 promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at the site of vascular injury