Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing GWAS Complexity

ABSTRACT Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 20151,2 from our groups.
Nuclear morphometry as a biomarker for bronchial intraepithelial neoplasia: Correlation with genetic damage and cancer development

Bronchial carcinomas are preceded by epithelial morphologic changes. The variation in interpretation of these grades of intraepithelial neoplasia makes it difficult to determine its natural history and utility of histopathology as a surrogate endpoint biomarker. The objective of this study was to quantitate morphologic changes of intraepitherlial neoplasia and validate its utility through correlation with histopathology, allelic loss, and cancer development.
The Fundamental Concepts of Metaphysics: World, Finitude, Solitude

First published in German in 1938 as volume 29/30 of Heidegger's collected works, "The Fundamental Concepts of Metaphysics" includes an extended treatment of the history of metaphysics and an elaboration of a philosophy of life and nature. Heidegger's concepts of organism, animal behaviour, and environment are uniquely developed and defined with intensity. This work, the text of Martin Heidegger's lecture course of 1929/30, is crucial for an understanding of Heidegger's transition from the major work of his early years, "Being and Time", to his later preoccupations with language, truth, and history.
Occupational cognitive requirements and late-life cognitive aging

Objective: To examine whether occupational cognitive requirements, as a marker of adulthood cognitive activity, are associated with late-life cognition and cognitive decline. Methods: Main lifetime occupation information for 7,637 participants aged >65 years of the Chicago Health and Aging Project (CHAP) was linked with standardized data on worker attributes and job characteristics from the Occupational Information Network (O*NET). Ratings of cognitive processes required in 10 work-related tasks were used to create a summary measure of occupational cognitive requirements (possible range 0–7). Multivariable-adjusted linear mixed models were used to estimate the association of occupational cognitive requirements score (OCRS) with cognitive function and rate of cognitive decline. Results: Higher OCRS corresponded to significantly better late-life cognitive performance at baseline in 1993 (p < 0.001) and to slower decline in global cognitive function over time (p = 0.004). Within a genotyped subsample (n = 4,104), the associations of OCRS with rate of cognitive decline did not differ significantly by APOE ε4 carriership (p = 0.11). Conclusions: Findings suggest that occupational cognitive requirements are associated with better cognition and a slower rate of cognitive decline in older age. Adulthood cognitive activity may contribute to cognitive reserve in late life.
The role of Swedish tonal word accents in children with language impairment

The present study was designed to examine the production of the Swedish tonal accents in children with language impairment and normal controls in order to verify previous findings. The productions of 25 children with linguistic impairment and their matched controls, aged 4;4–10;0 (mean age 5;11) were evaluated by ratings of fundamental frequency patterns, and by perceptual analysis by ten linguistically naive listeners to assess the distinctiveness of the accents. These methods give a more detailed description of the children's productions of tonal word accents. The results show that 60.8% of the children with language impairment have difficulties to produce the contrast of tonal word accents according to the F0 patterns. The difference in the rating of the F0 curves between the children with LI and their matched controls was significant. There is a significant positive correlation between the perceptual results and the F0‐rating, indicating that the better a child was perceived, the better his/her F0 production was rated. We conclude that the distinction between the tonal word accents is a difficult feature to acquire for Swedish children, which is shown both by acoustic and perceptual evaluations.
Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7‐nitro indazole

The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain NO synthase inhibitor 7‐nitro indazole (7‐NINA). Using 7‐NINA the first study of selective inhibition of the brain isoform of NO synthase on dopamine efflux in rat striatum was undertaken by use of in vivo microdialysis. Perfusion with 7‐NINA (1 mm) increased striatal dopamine efflux. The effect of 7‐NINA was partially antagonized (67%) by co‐perfusion with l‐arginine (1 mm), the precursor of NO formation in vivo. This suggests that 7‐NINA induces a competitive inhibition of NO synthase activity. These data show that endogenous NO has an inhibitory effect on striatal dopamine efflux in vivo.
A novel approach to compute the impedance matrix of a cochlear implant system incorporating an electrode-tissue interface based on finite element method

This paper proposes to use a new and realistic finite element model of a single turn human cochlea and cochlear implant electrode array with electrode-tissue interface to model the electric field imaging technique, which creates an impedance matrix. Due to discrepancy in the Warburg capacitor in the active and nonactive electrode contacts and electric power lost along the cochlea, the diagonal terms of the impedance matrix is larger than the off diagonal terms, which represent the impedance values of the nonactive electrode contacts. The impedance matrix from electric field imaging measurements is compared with the simulation results
In Early Childhood

Folk wisdoms, beliefs, religions, social and cultural characteristics, and psychologies of Thai people; roots of concepts about human life and birth; eastern wisdoms and modern western sciences; paradigms, philosophies, concepts, theories, and diversities of practices in child rearing and education; early childhood teacher spiritualities; morals, ethics, and professional ethics; approaches to self development practices; creative problem solving for sustainable development of young children well-being.
Morbidity reduction in critically ill trauma patients through use of a computerized insulin infusion protocol: a preliminary study.

BACKGROUND Recent data have demonstrated that intensive glycemic control during critical illness improves outcome. The purpose of our study was to evaluate the effect of a computerized hospital insulin protocol (CHIP) on glycemic control and outcome in critically ill trauma patients. METHODS Two, 6-month cohorts were compared, one 6 months prior to chip implementation (pre-CHIP) and one from the 6-month period after implementation (post-CHIP), using finger stick blood glucose values and demographic, injury severity, and outcome variables for adult patients with intensive care unit length of stay (LOS) > or =72 hours. Infectious morbidity was based upon the National Trauma Registry of the American College of Surgeons definitions. Differences between cohorts were assessed using Student's t test and Fisher's exact test for continuous and categorical variables. RESULTS The 129 pre- and 128 post-CHIP patients were well matched for demographics and injury severity. Significant reductions in mean finger stick blood glucose, rates of ventilator- associated pneumonia, central venous line infection, total infections, and all LOS categories were demonstrated in the post-CHIP cohort. However, mortality was significantly higher in the post-CHIP cohort. CONCLUSION This preliminary study demonstrates significant morbidity and LOS reductions with the use of a CHIP, but significantly increased mortality. Further prospective studies are necessary to assess the effects of intensive glycemic control on outcome after injury, particularly in sub populations who might be adversely affected.
Evidence-based sepsis therapy: a hospitalist perspective.

BACKGROUND Severe sepsis and septic shock are common and associated with a 30-50% mortality rate. Evidence-based therapies for severe sepsis supported by international critical care and infectious disease societies exist, but are inconsistently employed. METHODS The epidemiology and definitions of sepsis syndromes are reviewed; sepsis therapies supported by definitive studies in the field, along with the supporting literature, are summarized and presented from a hospitalist perspective. CONCLUSIONS Compelling observational data supports the importance of early, effective antibiotics. Well-designed randomized controlled trials and/or meta-analyses demonstrate the impact of activated protein C, early goal-directed therapy, stress-dose steroids, and intensive insulin in well-defined subgroups of patients. These therapies reduce the absolute mortality risk associated with severe sepsis by 9.5-16%; the corresponding numbers needed to treat to save one life are 6.25-10.5. While major trials are ongoing and the evidence for several sepsis therapies are limited to single trials, the available evidence indicates that appropriate use of these treatments can substantially reduce mortality from severe sepsis.
Validity and Reliability of the SF-36 Administered to Caregivers of Patients with Alzheimer’s Disease: Evidence from a South American Sample

Background: Being a caregiver of a patient with Alzheimer’s disease is associated with impaired health status and declines in health-related quality of life (HRQoL). This paper evaluates the reliability and validity of the Argentinean version of the Medical Outcomes Study Short-Form Health Survey (SF-36) among caregivers of patients with Alzheimer’s disease. Methods: Forty-eight caregivers of Alzheimer’s disease patients completed the SF-36, the Zarit Burden Interview (ZBI) and the Neuropsychiatric Inventory (NPI). Patients were evaluated for dementia severity using the Clinical Dementia Rating (CDR) and for cognitive status using the Mini Mental State Examination (MMSE). Results: The SF-36 scales demonstrated adequate-to-strong internal consistency (Cronbach’s alpha range: 0.72 to 0.92). Correlations between the SF-36 scales and the ZBI were moderate to strong (range: –0.19 to –0.79, all p < 0.01 expect for physical function). Significant correlations between the SF-36 scales and the CDR, MMSE and NPI were lower (range: –0.30 to –0.40, p < 0.001) and strongest in mental health-related scales of the SF-36. The SF-36 demonstrated good factorial validity. Conclusions: The Argentinean translation of the SF-36 is reliable and valid for use to measure the HRQoL of caregivers of patients with Alzheimer’s disease.
Effects of anti‐IL‐4 receptor monoclonal antibody on in vitro T cell cytokine levels: IL‐4 production by T cells from non‐atopic donors

IL‐4 is a pleiotropic cytokine which is involved in the development of atopic diseases. Only limited data exist on IL‐4 production in humans, and the relative contribution to atopy of either unbalanced IL‐4 production, or increased IL‐4‐responsiveness of target cells, is still unknown. The use of a MoAb to the IL‐4 receptor α‐chain (IL‐4Rα) enabled us to demonstrate that IL‐4 production in vitro is usually underestimated, due to in vitro consumption, even in cultures of purified T cells. When IL‐4 consumption was blocked, it became evident that CD80 and CD86 both provide effective costimulatory signals for high IL‐4 production. Moreover, we found that even stimulation with a soluble antigen (tetanus toxoid) induces IL‐4 production by T cells from healthy non‐atopic donors. Both sets of data imply that IL‐4 is not required for IL‐4 production by memory and/or effector T cells. Our data further show that endogenous IL‐4 activity modulates IL‐10 and interferon‐gamma production by T cells in opposite directions. The use of this receptor‐blocking antibody will thus be helpful for in vitro studies on IL‐4 regulation. Consumption of IL‐4 by different cell types during in vitro cultures might have interfered with previous attempts to quantify IL‐4 production by human T cells.
Emergentism and supervenience physicalism

A purely metaphysical formulation of physicalism is surprisingly elusive. One popular slogan is, ‘There is nothing over and above the physical’. Problems with this arise on two fronts. First, it is difficult to explain what makes a property ‘physical’ without appealing to the methodology of physics or to particular ways in which properties are known. This obviously introduces epistemic features into the core of a metaphysical issue. Second, it is difficult to cash out ‘over-and-aboveness’ in a way that is rigorous, metaphysically pure and extensionally apt for the purposes of the debate. In this paper I will touch on the first problem, but I wish to focus on the second. In particular, I will focus on the claim that supervenience theses cannot define physicalism because they allow classical emergentist dualism through the physicalist door [Horgan 1993; Kim 1998; Wilson 2005]. I will argue that when the relevant supervenience thesis is metaphysical, emergentism is excluded. Against recent arguments to the contrary, I maintain that this is the case even given necessitarianism about natural laws [Wilson 2005]. I will argue that a necessitarian with emergentist sympathies will be forced either into a type of quasi-panpsychism, where our basic physical properties contain the illicit seeds of mentality at their core, or she will be forced to admit that emergence laws are not necessary after all. Either way, the combination of necessitarianism and emergentism does not provide a counterexample to supervenience physicalism.
ON THE HISTORY OF ENGLISH THAN-COMPARATIVES

This paper, which takes the form of a critique of Seuren's theory of the comparative construction, is meant äs a contribution to typological and historical linguistics. In a number of publications, Seuren (e.g. 1973, 1978, 1984) has proposed that comparatives like (1) Jim is taller than Joe. should be analysed in terms of an underlying structure which crucially involves existential quantification over extents: (2) 3e: extent [Jim is tall to e ~[Joe is tall to ej (There is an extent e such that Jim is tall to e and Joe is not tall to e) Central to Seuren's discussion of (1) are the following Claims: (3) (a) Particle comparatives are related to coördinate structures. (b) Comparatives of inequality involve negation.
Some gait characteristics of below-knee amputees and their reflection on the ground reaction forces.

Human locomotion studies employing cinematography and force plates have been conducted during the last five decades with the goal of producing a clinically acceptable gait evaluation technique. The bulk of information contained in the kinetic studies was the major obstacle in achieving this goal. Our aim in this work was to explore the possibility of representing some locomotor abnormalities solely by their reflection on the ground reaction force characteristics. As a first stage towards the establishment of these relationships, the gait characteristics of below-knee amputees were examined.One hundred and thirty ground force test results as obtained on twenty three below-knee amputees were analysed. Different variables such as time durations of the various phases, peak forces, impulses, rate of change of the forces, and others, were examined. The conclusions suggest that some of these variables are suitable for evaluation of gait and some, such as small perturbations superimposed on the curve, may serve a.
The Link Between Workforce Health and Safety and the Health of the Bottom Line: Tracking Market Performance of Companies That Nurture a “Culture of Health”

Objective:To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. Methods:Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. Results:A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. Conclusions:Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.
Quantitative Computerized Tomography (QCT) versus Dual X-Ray Absorptiometry (DXA) in the Assessment of Bone Mineral Density of HIV-1 Infected Children

Bone studies of HIV-infected children using dual X-ray absorptiometry (DXA) suggest bone mineral density (BMD) abnormalities. Pediatric studies are often performed using DXA instead of computed tomography (CT), which accounts for 3-dimensional differences in bone size of growing children. We evaluated whether CT would match DXA measurements in this population. For this purpose, the BMD of 16 perinatally HIV-infected patients, ages 6 to 22 was assessed. Subjects were matched by age, gender, and race to controls. BMD was assessed via DXA and QCT. Clinical anthropometric data, body mass index, immunologic and virologic parameters and laboratory markers for osteoblastic and osteoclastic activity were performed. No statistically significant differences in age and anthropometric parameters between subjects and controls were found. Individual CT and DXA z-scores were significantly different when subjects were evaluated as a group (p = 0.0002) or when males and females were analyzed independently (p = 0.001 and 0.03). DXA z-scores were below 1 SD, while CT z-scores were above the mean. 31% of subjects were identified as having poor bone mineralization by DXA while none had osteopenia/osteoporosis by CT. There was no correlation between immunologic/virologic parameters and BMD by either method. Increased osteoclastic activity was noted in 10 patients receiving tenofovir. In summary, decreased BMD diagnosed by DXA in pediatric HIV-infected subjects was not confirmed by CT. Increased bone turnover in patients on tenofovir was suggested by laboratory markers. Prospective studies using CT as the imaging standard are needed for evaluation of bone mineral changes in HIV-infected children.
Functional projections, markedness, and “root infinitives” in early child Greek

The aim of this paper is to determine whether there is an equivalent Root Infinitive stage for children acquiring a language which does not have an infinitive construction, namely Modern Greek. We find that in the typical Root Infinitive contexts Greek children use a verb form involving the suffix -i, which corresponds to the 3rd person singular suffix, as well as to a participial form. We argue that the data are best explained by treating the -i form as the participle, thus suggesting that the putative congener of the Root Infinitive need not be an infinitive. Under Rizzi's (1994) approach, we would in fact expect various non-finite verb forms to be attested in the main clauses of the youngest speakers of various languages
Trust in Internet Shopping: A Proposed Model and Measurement Instrument

Despite the phenomenal growth of Internet users in recent years, the penetration rate of Internet shopping is still very low and one of most often cited reasons is the lack of consumers’ trust [e.g. Hoffman et al., 1999]. Although trust is an important concept in Internet shopping, there is a paucity of theory-guided empirical research in this area. In this paper, a theoretical model is proposed for investigating the nature of trust in the specific context of Internet shopping. In this model, consumers’ trust in Internet shopping is affected by two groups of antecedent factors, namely, “trustworthiness of Internet vendors” and “external environment”. In addition, the effects of these factors on trust are moderated by the consumers’ propensity to trust. Trust, in turn, reduces consumers’ perceived risk in Internet shopping. As a step towards the rigorous testing of the model, a 30-item measurement instrument has been developed with its reliability and validity empirically tested. This research contributes to the development of trust theory in e-commerce and provides a validated instrument for the measurement of various important trust related constructs.
Integrative Approaches for the Identi fi cation and Localization of Specialized Metabolites in Tripterygium Roots 1 [ OPEN ]

Members of the genus Tripterygium are known to contain an astonishing diversity of specialized metabolites. The lack of authentic standards has been an impediment to the rapid identification of such metabolites in extracts. We employed an approach that involves the searching of multiple, complementary chromatographic and spectroscopic data sets against the Spektraris database to speed up the metabolite identification process. Mass spectrometry-based imaging indicated a differential localization of triterpenoids to the periderm and sesquiterpene alkaloids to the cortex layer of Tripterygium roots. We further provide evidence that triterpenoids are accumulated to high levels in cells that contain suberized cell walls, which might indicate a mechanism for storage. To our knowledge, our data provide first insights into the cell type specificity of metabolite accumulation in Tripterygium and set the stage for furthering our understanding of the biological implications of specialized metabolites in this genus.