Miracle-dz/UniFAR-FTUs huggingface dataset:
Orthographic processing: A ‘mid-level’ vision of reading: The 44th Sir Frederic Bartlett Lecture

I will describe how orthographic processing acts as a central interface between visual and linguistic processing during reading, and as such can be considered to be the ‘mid-level vision’ of reading research. In order to make this case, I first summarize the evidence in favour of letter-based word recognition before examining work investigating how orthographic similarities among words influence single word reading. I describe how evidence gradually accumulated against traditional measures of orthographic similarity and the associated theories of orthographic processing, forcing a reconsideration of how letter-position information is represented by skilled readers. Then, I present the theoretical framework that was developed to explain these findings, with a focus on the distinction between location-specific and location-invariant orthographic representations. Finally, I describe work extending this theoretical framework in two main directions: first, to the realm of reading development, with the aim to specify the key changes in the processing of letters and letter strings that accompany successful learning to read, and second, to the realm of sentence reading, in order to specify how orthographic information can be processed across several words in parallel, and how skilled readers keep track of which letters belong to which words.
Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study.

OBJECTIVE To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. METHODS We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. RESULTS During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. CONCLUSION Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.
Dysphagia following Stroke

Background: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. Methods: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. Results: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). Conclusions: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.
Flow Cytometry-Assisted Cloning of Specific Sequence Motifs from Complex 16S rRNA Gene Libraries

ABSTRACT A flow cytometry method was developed for rapid screening and recovery of cloned DNA containing common sequence motifs. This approach, termed fluorescence-activated cell sorting-assisted cloning, was used to recover sequences affiliated with a unique lineage within the Bacteroidetes not abundant in a clone library of environmental 16S rRNA genes.
Visual risk factors for falls in older people.

OBJECTIVES To determine the tests most predictive of falls in community-dwelling older people from a range of visual screening tests (high and low contrast visual acuity, edge contrast sensitivity, depth perception, and visual field size). To determine whether one or more of these visual measures, in association with measures of sensation, strength, reaction time, and balance, can accurately predict falls in this group. DESIGN Prospective cohort study of 12 months duration. SETTING Falls and Balance Laboratory, Prince of Wales Medical Research Institute. PARTICIPANTS 156 community-dwelling men and women age 63 to 90 (mean age 76.5, standard deviation = 5.1). MEASUREMENTS Screening tests of vision, sensation, strength, reaction time and balance, falls. RESULTS Of the 148 subjects available at follow-up, 64 (43.2%) reported falling, with 32 (21.7%) reporting multiple falls. Multiple fallers had decreased vision, as indicated by all visual tests, with impaired depth perception, contrast sensitivity, and low-contrast visual acuity being the strongest risk factors. Subjects with good vision in both eyes had the lowest rate of falls, whereas those with good vision in one eye and only moderate or poor vision in the other eye had elevated falling rates-equivalent to those with moderate or poor vision in both eyes. Discriminant analysis revealed that impaired depth perception, slow reaction time, and increased body sway on a compliant surface were significantly and independently associated with falls. These variables correctly classified 76% of the cases, with similar sensitivity and specificity. CONCLUSION The study findings indicate that impaired vision is an important and independent risk factor for falls. Adequate depth perception and distant-edge-contrast sensitivity, in particular, appear to be important for maintaining balance and detecting and avoiding hazards in the environment.
Rethinking Historical Trauma: Narratives of Resilience

There is significant variation in how people experience, emplot and intergenerationally transmit trauma experiences. Despite this variation, the literature rarely illustrates alternative manifestations or resilient responses to the construct of historical trauma. Based upon person-centered ethnographic research, this article highlights how a four-generation American Indian family contextualizes historical trauma and, specifically, how they frame their traumatic past into an ethic that functions in the transmission of resilience strategies, family identity, and as a framework for narrative emplotment. In conclusion, the author clarifies the distinction between historical trauma — the precipitating conditions or experiences — and the historical trauma response — the pattern of diverse responses that may result from exposure to historical trauma.
Ultrastructure of the Retina in Adult Neuronal Ceroid Lipofuscinosis

A 33-year-old woman died of biopsy-proven adult neuronal ceroid lipofuscinosis (NCL) or Kufs’ disease marked by fingerprint and curvilinear lipopigments in neural and nonneural cell types. She had never experienced visual impairment or shown electroretinographic abnormalities. At autopsy, her retina appeared intact without degeneration at the light-microscopic level, but nerve cells in different layers were loaded with lipopigments of the granular type. This appears to be the third ultrastructural study of the retina in a patient with adult NCL, a former one showing preservation of the retina, another retinal degeneration. Thus, only further molecular genetic data will clarify the nosology of adult NCL with and without retinal degeneration.
Facilitating early recovery of bowel motility after colorectal surgery: a systematic review.

AIMS AND OBJECTIVES To determine how restored gastrointestinal motility can be accelerated after colorectal surgery. BACKGROUND Regaining normal bowel functions after surgery is described as unexpectedly problematic. Postoperative ileus is expected after all surgery where the peritoneum is entered, and the length of surgery has little or no impact in terms of the duration of Postoperative ileus. There is some speculation about the best way to facilitate bowel motility after colorectal surgery. DESIGN A systematic review. METHOD The computerised databases Medline, Scopus and CINAHL were searched to locate randomised, controlled trials by using the following keywords: colorectal surgery, postoperative ileus, recovery of function and gastrointestinal motility. The systematic search was limited to studies published between January 2002-January 2012. Reference lists were also searched manually. RESULTS A total of 34 randomised, controlled trials were included in the review. Recovery of gastrointestinal motility was accelerated when one of the following forms of treatment was administered: probiotics, early feeding in combination with multimodal regimens, pentoxifylline, flurbiprofen, valdecoxib, ketorolac, clonidine, ropivacaine, lidocaine or spinal analgesia. Gum chewing, preoperative carbohydrate loading, bisacodyl and Doppler-guided fluid management have an uncertain effect on bowel motility. The use of nonpharmacological interventions, intrathecal morphine, restricted fluid therapy and choline citrate yielded no significant acceleration in bowel motility. CONCLUSIONS A multimodal treatment, where the use of morphine is restricted, seems to be the best way to accelerate the recovery of gastrointestinal bowel motility. However, more studies are required to optimise the multimodal protocol. RELEVANCE TO CLINICAL PRACTICE The early return of bowel functions leads to quicker overall postoperative recovery, which may ease patient discomfort and decrease hospitalisation costs.
Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

Background. Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. Methods. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. Results. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. Conclusion. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended.
A study of pathologic risk factors in postchemoreduced, enucleated specimens of advanced retinoblastomas in a developing country.

CONTEXT Advanced cases of retinoblastoma are treated with chemoreduction followed by enucleation. Further adjuvant therapy is recommended in patients with known pathologic risk factors (PRFs). OBJECTIVES To determine the PRFs in enucleated specimens after chemoreduction and their association for adverse events of recurrence, metastasis, or death. DESIGN This was a retrospective study of 77 enucleation specimens from patients treated between January 2000 and September 2008 with prior chemoreduction that were accessioned in the pathology department of a tertiary referral cancer center with an average follow-up of 24 months. Various PRFs were noted and their association with the development of an adverse event was recorded. RESULTS Of 77 patients, (male to female ratio, 51∶26), the incidence of overall PRF was 51.9%, and retrolaminar optic nerve invasion (32.5%), optic nerve cut margin (12.9%), massive choroidal invasion (26%), scleral invasion (23.4%), vitreous seedings (44.2%), and anterior segment invasion (20.8%). Undifferentiated tumor (>60%) was seen in 60.3% of cases (41 of 68 patients with differentiation available). Adverse event occurred in 18 of 72 patients with available follow-up (25%). Retrolaminar optic nerve invasion, optic nerve cut margin involvement, and scleral invasion were independent prognostic factors predicting the occurrence of an adverse event. Undifferentiated tumor (>60%) was a significant risk factor in univariate analysis, which is the unique feature in this study. CONCLUSIONS Classic PRF with the addition of a predominant presence from the undifferentiated component were associated with adverse outcomes in retinoblastoma treated with anterior chemotherapy. The latter may represent chemoresistant clones and more intensive adjuvant chemotherapy may be warranted in these patients.
Association of physical examination with pulmonary artery catheter parameters in acute lung injury *

OBJECTIVE To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. DESIGN Retrospective study. SETTING Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. PATIENTS Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. INTERVENTIONS Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. MEASUREMENTS We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. MEASUREMENTS AND MAIN RESULTS Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%,specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and high central venous pressure, but these correlations were not found to be clinically useful. CONCLUSIONS In this subset of patients with acute lung injury, there is a high prior probability that cardiac index and mixed venous oxygen saturation are normal and physical examination findings of ineffective circulation are not useful for predicting low cardiac index or mixed venous oxygen saturation. Central venous oxygen saturation <70% does not accurately predict mixed venous oxygen saturation <60%, but a central venous oxygen saturation >or=70% may be useful to exclude mixed venous oxygen saturation <60%.
The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges.

PURPOSE To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. METHODS Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9% saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. RESULTS No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. CONCLUSION Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.
Optimal Treatment Strategies in the Context of ‘Treatment for Prevention’ against HIV-1 in Resource-Poor Settings

An estimated 2.7 million new HIV-1 infections occurred in 2010. `Treatment-for-prevention’ may strongly prevent HIV-1 transmission. The basic idea is that immediate treatment initiation rapidly decreases virus burden, which reduces the number of transmittable viruses and thereby the probability of infection. However, HIV inevitably develops drug resistance, which leads to virus rebound and nullifies the effect of `treatment-for-prevention’ for the time it remains unrecognized. While timely conducted treatment changes may avert periods of viral rebound, necessary treatment options and diagnostics may be lacking in resource-constrained settings. Within this work, we provide a mathematical platform for comparing different treatment paradigms that can be applied to many medical phenomena. We use this platform to optimize two distinct approaches for the treatment of HIV-1: (i) a diagnostic-guided treatment strategy, based on infrequent and patient-specific diagnostic schedules and (ii) a pro-active strategy that allows treatment adaptation prior to diagnostic ascertainment. Both strategies are compared to current clinical protocols (standard of care and the HPTN052 protocol) in terms of patient health, economic means and reduction in HIV-1 onward transmission exemplarily for South Africa. All therapeutic strategies are assessed using a coarse-grained stochastic model of within-host HIV dynamics and pseudo-codes for solving the respective optimal control problems are provided. Our mathematical model suggests that both optimal strategies (i)-(ii) perform better than the current clinical protocols and no treatment in terms of economic means, life prolongation and reduction of HIV-transmission. The optimal diagnostic-guided strategy suggests rare diagnostics and performs similar to the optimal pro-active strategy. Our results suggest that ‘treatment-for-prevention’ may be further improved using either of the two analyzed treatment paradigms.
Structural and Functional Analysis of Coxsackievirus A9 Integrin αvβ6 Binding and Uncoating

ABSTRACT Coxsackievirus A9 (CVA9) is an important pathogen of the Picornaviridae family. It utilizes cellular receptors from the integrin αv family for binding to its host cells prior to entry and genome release. Among the integrins tested, it has the highest affinity for αvβ6, which recognizes the arginine-glycine-aspartic acid (RGD) loop present on the C terminus of viral capsid protein, VP1. As the atomic model of CVA9 lacks the RGD loop, we used surface plasmon resonance, electron cryo-microscopy, and image reconstruction to characterize the capsid-integrin interactions and the conformational changes on genome release. We show that the integrin binds to the capsid with nanomolar affinity and that the binding of integrin to the virion does not induce uncoating, thereby implying that further steps are required for release of the genome. Electron cryo-tomography and single-particle image reconstruction revealed variation in the number and conformation of the integrins bound to the capsid, with the integrin footprint mapping close to the predicted site for the exposed RGD loop on VP1. Comparison of empty and RNA-filled capsid reconstructions showed that the capsid undergoes conformational changes when the genome is released, so that the RNA-capsid interactions in the N termini of VP1 and VP4 are lost, VP4 is removed, and the capsid becomes more porous, as has been reported for poliovirus 1, human rhinovirus 2, enterovirus 71, and coxsackievirus A7. These results are important for understanding the structural basis of integrin binding to CVA9 and the molecular events leading to CVA9 cell entry and uncoating.