Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on the role of genetics in the onset of age-related macular degeneration

Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century.
Predictors of cognitive decline in older people with diabetes

This is an uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association, publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care in print and online at http://care.diabetesjournals. org. Diabetes Care Publish Ahead of Print, published online July 23, 2008
Cerebellar Medulloblastoma with Multiple Differentiation in a Dog

A 4-year-old female, spayed Border Collie Dog was brought to the Veterinary Medical Teaching Hospital for evaluation of a progressive head tilt and ataxia that were unresponsive to therapy. Neurologic examination localized a right-sided lesion. The owner refused additional diagnostic tests, and necropsy was performed after euthanasia. Gross findings included atrophy of the temporal muscles and a moderately well delineated, 2.5- X 1.5- X 1.0-cm, gray soft-tissue mass compressing the right cerebellar hemisphere and dorsal hindbrain, resulting in massive dilatation of the lateral, third, and fourth ventricles and hydrocephalus. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal to fusiform cells with typical morphologic characteristics of medulloblastoma and interspersed areas containing myelinated axons and cells with glial and neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with glial and neuronal differentiation.
Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling

ABSTRACT Introduction: Drug-induced liver injury (DILI) is a significant threat to human health and a major problem in drug development. It is hard to predict due to its idiosyncratic nature and which does not show up in animal trials. Hepatic adaptive stress response pathway activation is generally observed in drug-induced liver injury. Dynamical pathway modeling has the potential to foresee adverse effects of drugs before they go in trial. Ordinary differential equation modeling can offer mechanistic insight, and allows us to study the dynamical behavior of stress pathways involved in DILI. Areas covered: This review provides an overview on the progress of the dynamical modeling of stress and death pathways pertinent to DILI, i.e. pathways relevant for oxidative stress, inflammatory stress, DNA damage, unfolded proteins, heat shock and apoptosis. We also discuss the required steps for applying such modeling to the liver. Expert opinion: Despite the strong progress made since the turn of the century, models of stress pathways have only rarely been specifically applied to describe pathway dynamics for DILI. We argue that with minor changes, in some cases only to parameter values, many of these models can be repurposed for application in DILI research. Combining both dynamical models with in vitro testing might offer novel screening methods for the harmful side-effects of drugs.
Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months

Background: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. Methods: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. Results: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. Interpretation: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.
Long-Term Demographic Forecasts and Implications for Health Care Resources and Repurposing

We examine long-term demographic forecasts to determine whether increases in the senior population will be followed by a decrease once the baby-boom generation passes. Planners may therefore need to flexibly assign resources to allow for future repurposing of investments. Forecasts in the U.S. and Canada indicate that the number of seniors in the population will plateau by the year 2045 with levels roughly maintained until at least 2060; thus, repurposing may be unnecessary. Increases in life-expectancy, immigration age structures, and echoes of the baby-boom generation in later years are expected to help maintain this plateau. While there is no observable decrease in the senior population by 2060, there is uncertainty around the expected rate of decline in health of this generation. Depending on this trajectory, community-level social supports could play a large role in maintaining senior health and independence as long as possible.
Constructing Agency: The Role of Language

Is agency a straightforward and universal feature of human experience? Or is the construction of agency (including attention to and memory for people involved in events) guided by patterns in culture? In this paper we focus on one aspect of cultural experience: patterns in language. We examined English and Japanese speakers’ descriptions of intentional and accidental events. English and Japanese speakers described intentional events similarly, using mostly agentive language (e.g., “She broke the vase”). However, when it came to accidental events English speakers used more agentive language than did Japanese speakers. We then tested whether these different patterns found in language may also manifest in cross-cultural differences in attention and memory. Results from a non-linguistic memory task showed that English and Japanese speakers remembered the agents of intentional events equally well. However, English speakers remembered the agents of accidents better than did Japanese speakers, as predicted from patterns in language. Further, directly manipulating agency in language during another laboratory task changed people’s eye-witness memory, confirming a possible causal role for language. Patterns in one’s linguistic environment may promote and support how people instantiate agency in context.
Planck intermediate results V

Taking advantage of the all-sky coverage and broad frequency range of the Planck satellite, we study the Sunyaev-Zeldovich (SZ) and pressure profiles of 62 nearby massive clusters detected at high significance in the 14-month nominal survey. Careful reconstruction of the SZ signal indicates that most clusters are individually detected at least out to R500. By stacking the radial profiles, we have statistically detected the radial SZ signal out to 3 x R500, i.e., at a density contrast of about 50-100, though the dispersion about the mean profile dominates the statistical errors across the whole radial range. Our measurement is fully consistent with previous Planck results on integrated SZ fluxes, further strengthening the agreement between SZ and X-ray measurements inside R500. Correcting for the effects of the Planck beam, we have calculated the corresponding pressure profiles. This new constraint from SZ measurements is consistent with the X-ray constraints from XMM-Newton in the region in which the profiles overlap (i.e., [0.1-1]R500), and is in fairly good agreement with theoretical predictions within the expected dispersion. At larger radii the average pressure profile is slightly flatter than most predictions from numerical simulations. Combining the SZ and X-ray observed profiles into a joint fit to a generalised pressure profile gives best-fit parameters [P0, c500, gamma, alpha, beta] = [6.41, 1.81, 0.31, 1.33, 4.13]. Using a reasonable hypothesis for the gas temperature in the cluster outskirts we reconstruct from our stacked pressure profile the gas mass fraction profile out to 3 x R500. Within the temperature driven uncertainties, our Planck constraints are compatible with the cosmic baryon fraction and expected gas fraction in halos.
Children’s Executive Function Attenuate the Link Between Maternal Intrusiveness and Internalizing Behaviors at School Entry

The goal of this study was to examine the independent and interactive roles of harsh-intrusive maternal behaviors and children’s executive function in the development of internalizing behaviors across the first years of school. A diverse sample (58% African American, 42% European American) of 137 children (48% female) was followed from kindergarten (age 5 years) through school entry (ages 6–7 years). At age 5, maternal harsh-intrusive parenting behaviors were rated from a mother–child structured play task, and children completed 3 executive function tasks that measured inhibitory control, working memory, and attention set-shifting. Teachers reported on children’s internalizing behaviors at ages 5, 6, and 7. Harsh-intrusive parenting behaviors at age 5 years were positively related to internalizing behaviors in the first years of school, whereas high executive function abilities at age 5 years were related to lower internalizing behaviors in the first years of school. In addition, executive function buffered the association between parenting behaviors and internalizing behaviors such that the link between harsh-intrusive parenting and child internalizing behaviors was evident only among children with low executive function and not among children with high executive function. Interventions that focus on reducing negative parenting behaviors and improving children’s executive function may prevent internalizing behaviors from increasing during times of social and academic challenge.
Who Believes Electronic Games Cause Real World Aggression?

Electronic games have rapidly become a popular form of human recreation, and the immersive experiences they provide millions have led many to voice concerns that some games, and violent ones in particular, may negatively impact society. Increasingly heated debates make it clear that gaming-related aggression is a topic that elicits strong opinions. Despite a complex and growing literature concerned with violent games, little is known empirically about why some ardently believe, whereas others dismiss, notions that this form of leisure is a source of aggression. The present research recruited three nationally representative samples to investigate this understudied topic. Results showed that belief was normally distributed across the population, prominent among demographic cohorts who did not grow up with games and those who lack concrete gaming experience. Results are discussed in the context of this developing research area, wider social science perspectives, and the place of electronic games in society.
Review of TDNN (time delay neural network) architectures for speech recognition

The TDNN architecture for speech recognition is described, and its recognition performance for Japanese phonemes and phrases is explained. In comparative studies, it is shown that the TDNN yields superior phoneme recognition performance. The TDNN optimized for phoneme recognition, however, does not necessarily result in optimized word or phrase recognition performance, as overfitting to the specific phoneme data or recording conditions may occur. Care must therefore be taken to achieve robust integration, and several studies toward this goal are reported. <<ETX>>
Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography

Abstract Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI) and a source of significantly increased short- and long-term mortality. Studies of large cohorts have revealed that more than half of these cases are in subjects undergoing cardiac catheterization and intra-arterial coronary angiography, and nearly a third follow computed tomography (CT) scans. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early predictive troponin-like biomarker for AKI. Its role in the timely diagnosis of CIN has already been examined in adults and children undergoing coronary angiography and a meta-analysis revealed a very good performance of plasma or urine NGAL in the prediction of CIN. Much of these data have been extrapolated to patients receiving intravenous (IV) contrast agent for CT scans, although major differences in patient populations, contrast volume administered and intra-procedural complications between the two settings exist. In this context, a recent prospective study by our group evaluated plasma NGAL, measured using standardized Τriage® NGAL test (Biosite Incorporated, San Diego, CA) at baseline and 6-h post-procedure, for early detection of CIN among hospitalized patients undergoing elective contrast-enhanced CT. CIN, defined as an increase in serum creatinine (SCr) of >25% or >0.5 mg/dL from baseline within 48-h post-procedure, was found in 8.51% of subjects. In contrast, significant elevation of plasma NGAL was found at 6-h post-procedure with excellent performance characteristics. This review presents the current status of NGAL in the prediction of CIN after IV contrast administration among hospitalized patients undergoing elective contrast-enhanced CT.
Townshipnet: a localized hybrid TVWS-WiFi and cloud services network

This paper describes a network architecture to provide low cost last mile access and cloud services for local content sharing in a poorly resourced township environment. We describe how ICT solutions are developed in close partnership with the local community who will benefit from the interventions. We analyze the data usage patterns of mobile users in the township to provide us with a real understanding of the needs of the community. This data usage analysis is used to inform the design of the network and of the localized cloudlet services. The network consists of hybrid TV White Space and WiFi backhaul and WiFi public access points.
A systematic review of evidence on the links between patient experience and clinical safety and effectiveness

Objective To explore evidence on the links between patient experience and clinical safety and effectiveness outcomes. Design Systematic review. Setting A wide range of settings within primary and secondary care including hospitals and primary care centres. Participants A wide range of demographic groups and age groups. Primary and secondary outcome measures A broad range of patient safety and clinical effectiveness outcomes including mortality, physical symptoms, length of stay and adherence to treatment. Results This study, summarising evidence from 55 studies, indicates consistent positive associations between patient experience, patient safety and clinical effectiveness for a wide range of disease areas, settings, outcome measures and study designs. It demonstrates positive associations between patient experience and self-rated and objectively measured health outcomes; adherence to recommended clinical practice and medication; preventive care (such as health-promoting behaviour, use of screening services and immunisation); and resource use (such as hospitalisation, length of stay and primary-care visits). There is some evidence of positive associations between patient experience and measures of the technical quality of care and adverse events. Overall, it was more common to find positive associations between patient experience and patient safety and clinical effectiveness than no associations. Conclusions The data presented display that patient experience is positively associated with clinical effectiveness and patient safety, and support the case for the inclusion of patient experience as one of the central pillars of quality in healthcare. It supports the argument that the three dimensions of quality should be looked at as a group and not in isolation. Clinicians should resist sidelining patient experience as too subjective or mood-oriented, divorced from the ‘real’ clinical work of measuring safety and effectiveness.
Jitter and recovery rate of a triggered spark gap with high pressure gas mixtures

Recent attention to impulse antenna phased arrays has necessitated the need to develop a reliable high voltage, high repetition rate switch that will operate with ultra low jitter. The ideal jitter of such a switch would be a small fraction of the risetime in order to synchronize the array to steer and preserve the risetime of the radiated pulse. This paper presents the impact, gases and gas mixtures have on switch performance which includes recovery rate and in particular, jitter. A 50 Ω, 1 nF pulse forming line is charged to 30 kV and provides the low inductance voltage source to test the different gases. Triggering is provided by an SOS voltage source that supplies ≫100 kV, 10 ns risetime pulses at a rep rate up to 1 kHz in burst mode. A hermetically sealed spark gap with a Kel-F lining is used to house the switch and high pressure gas. The system contains a high pressure gas mixing chamber that can mix various gases up to 2000 psi. Gases tested include dry air, H2, N2, and SF6.
Central Conduction Time of Magnetic Brain Stimulation in Attention-Deficit Hyperactivity Disorder

Twenty-seven children and adolescents aged 4 to 18 years, fulfilling the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for attention-deficit hyperactivity disorder, were included in this study. The diagnosis was determined by a pediatric neurologist and a psychologist examined all 27 subjects with tests that included the Wechsler Intelligence Scale for Children-Revised (WISC-R) and reading, writing, handedness, personality, and anxiety scores. Subjects with histories of epilepsy, head injury, drug abuse, or psychotic disorders were excluded. Culturally based causes or emotional disorders were also excluded. Transcranial magnetic stimulation was performed on all subjects, with recording of the motor evoked potential at the biceps brachii. Central motor conduction time was calculated by cervical root stimulation. Due to shape variability, the amplitude of the motor responses was not measured in the study. The mean value of central conduction time in the subjects was very significantly increased (P < .001) compared to that in a group of normal controls, case-matched for IQ, age, and sex. A central motor conduction time greater than 12 ms indicates abnormality. A second finding in the subjects was the significant difference of central conduction time on the side-to-side stimulation (P = .03). These findings are correlated with delay in the maturation of the corticomotoneuronal system and might provide neurophysiologic data for diagnosis. (J Child Neurol 2000;15:723-728).
Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone

OBJECTIVES To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). METHODS Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n=10) or cerebellar degeneration (PCD) with anti-Yo Abs (n=7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS⩽3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS⩾4). RESULTS Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS⩾4, none improved. Of the nine patients with RS⩽3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. CONCLUSIONS This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.