Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocular cyclotorsion during customized laser ablation.

PURPOSE To compare the measured difference and degree of cyclotorsion in eyes undergoing customized laser ablation between the time of wavefront measurement and laser refractive surgery. METHODS The degree of cyclotorsion was measured in 1019 consecutive eyes of 732 patients who underwent wavefront-guided corneal ablation for the treatment of myopia with or without astigmatism with the Alcon LADARVision excimer laser. Prior to obtaining the wavefront measurement, the horizontal axis of each eye was marked. Cyclotorsional alignment was measured on the supine patient prior to beginning the laser. RESULTS The predominant trend was for excyclotorsion. The total range of torsion in degrees was 0.5 degrees to 17.5 degrees (mean: 4.05 +/- 2.9 degrees). Cyclotorsion > 2 degrees occurred in 68% of all eyes. In the right eyes, 83% excyclotorted, 14% incyclotorted, and 3% displayed no torsion. In the left eyes, 62% excyclotorted, 34% incyclotorted, and 4% exhibited no torsion. In a subset of 112 patients undergoing simultaneous bilateral surgery, 46% displayed bilateral excyclotorsion and 1.7% displayed bilateral incyclotorsion. CONCLUSIONS In this study, the majority of eyes had a low to moderate amount of cyclotorsion observed with the change of orientation from seated to supine position. Excyclotorsion was the predominant pattern. Proper registration prior to wavefront-guided corneal ablation is essential for proper correction of astigmatism and higher order aberrations to achieve optimal visual outcomes.
Audit Market Response to PCAOB Censures of US Big 4 Firms

Abstract Subsequent to the first-ever Public Company Accounting Oversight Board (PCAOB) censure of a US Big 4 firm (Deloitte) in December 2007, there were two other PCAOB US Big 4 firm censures as of 2016 year-end. We examine whether these two post-2007 PCAOB censures of US Big 4 firms conveyed new information to the audit market. For both censures, we find little or no evidence of any change in the factual audit quality of the censured firm over a three-year window surrounding the censure. Our findings suggest that the quality control deficiencies (identified during inspection of specific audit engagements) that triggered the PCAOB censure were isolated occurrences rather than systemic to the firm at large, i.e., the censures do not imply an impairment in the US Big 4 firm's overall factual audit quality. We also find that the negative response of investors and audit committees documented in prior research for the 2007 Deloitte censure disappeared for the later US Big 4 firm censures. Given that the PCAOB inspects (and can censure) non-US auditors who audit US-listed foreign companies, our findings are of potential interest to regulators, investors and audit committees outside the US.
Site-directed recombination via bifunctional PNA–DNA conjugates

Site-specific DNA binding molecules offer the potential for genetic manipulation of mammalian cells. Peptide nucleic acids (PNAs) are a DNA mimic in which the purine and pyrimidine bases are attached to a polyamide backbone. PNAs bind with high affinity to single-stranded DNA via Watson–Crick base pairing and can form triple helices via Hoogsteen binding to DNA/PNA duplexes. Dimeric bis-PNAs capable of both strand invasion and triplex formation can form clamp structures on target DNAs. As a strategy to promote site-directed recombination, a bis-PNA was coupled to a 40-nt donor DNA fragment homologous to an adjacent region in the target gene. The PNA–DNA conjugate was found to mediate site-directed recombination with a plasmid substrate in human cell-free extracts, resulting in correction of a mutation in a reporter gene at a frequency at least 60-fold above background. Induced site-specific recombination was also seen when the bis-PNA and the donor DNA were co-mixed without covalent linkage. In addition, the bis-PNA and the bis-PNA–DNA conjugate were found to induce DNA repair specifically in the target plasmid. Both the PNA-induced recombination and the PNA-induced repair were found to be dependent on the nucleotide excision repair factor, XPA (xeroderma pigmentosum complementation group A protein). These results suggest that the formation of a PNA clamp on duplex DNA creates a helical distortion that strongly provokes DNA repair and thereby sensitizes the target site to recombination. The ability to promote recombination in a site-directed manner using PNA–DNA conjugates may provide a useful strategy to achieve targeted correction of defective genes.
Metabolic Syndrome Is Associated With Silent Ischemic Brain Lesions

Background and Purpose— Metabolic syndrome (MetS) is a recognized risk factor for stroke, but it is unclear whether MetS is also related to subclinical ischemic lesions. We examined the association of MetS with the prevalence of silent brain infarction, periventricular hyperintensity, and subcortical white matter lesions in healthy adults. Methods— We conducted a cross-sectional study in 1151 Japanese healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS was diagnosed using the criteria by the National Cholesterol Education Adult Treatment Panel III. Results— After adjusting for age and other factors, MetS was significantly associated with silent brain infarction, periventricular hyperintensity and subcortical white matter lesions. Among the MetS components, elevated blood pressure was commonly associated with all types of lesions. Dyslipidemia and elevated fasting glucose levels were associated with subcortical white matter lesions and periventricular hyperintensities, respectively. Positive trends were observed between the number of MetS components and prevalence of silent lesions. Conclusions— MetS is associated with the prevalence of silent lesions independent of other risk factors. The clustering of MetS components tends to increase the prevalence of silent lesions.
Leukemia‐Associated Lymph Node Infiltrates of Plasmacytoid Monocytes (So‐called Plasmacytoid T‐cells) Evidence for Two Distinct Histological and Immunophenotypical Patterns

The medium-sized mononuclear cell with plasmacytoid features, formerly known as “T-associated plasma cell” or “plasmacytoid T cell,” has recently been shown to express several myelomonocyte and monocyte-macrophage associated antigens, suggesting a monocytic origin, and it has been renamed “plasmacytoid monocyte. ” The present study describes the clinical and pathological features of two patients with generalized lymphadenopathy and leukemia (chronic myelomonocytic leukemia in Case 1, and acute non-B, non-T lymphoblastic leukemia in Case 2), and whose lymph node biopsies showed large numbers of plasmacytoid monocytes associated with the leukemic infiltrates. Case 1 was strikingly similar to three previously reported cases of so-called “plasmacytoid T cell” lymphoma, all associated with a myeloproliferative disorder. In our case, the destructive growth pattern of the plasmacytoid monocytes and the de novo expression of CD5 on these cells favored their neoplastic nature; the sharing of some markers of plasmacytoid monocytes with the myelomonocytic infiltrate suggested they were part of the tumoral proliferation. In Case 2, plasmacytoid monocytes displayed an immunophenotype guide similar to that reported in reactive conditions and were antigenically unrelated to the leukemic cells; plasmacytoid monocyte clusters occurred also in the lymphoid parenchyma spared by the leukemic infiltrate. These findings led us to interpret the large numbers of plasmacytoid monocytes in this second case as a tumor-associated host reaction.
Leadership for Learning as Experience: Introducing the Use of Vignettes for Research on Leadership Experiences in Schools

Research on the link between educational leadership and student learning employs a variety of quantitative and qualitative research designs. Surprisingly, there are relatively few studies on methods for researching educational leadership practices. This article addresses this gap in research and discusses how the experiences of different participants can constitute potential starting points for learning processes. This leads to the question, how and to what extent the educational leadership practices manifest in students’ experiences and how “Leadership for Learning as Experience” can be empirically researched. The phenomenologically oriented vignette as research method for studying educational leadership practices will be introduced. Vignettes are narratives that are based on the experiences of participants. In vignettes, the co-experienced observations in the field are captured in form of vivid narratives. Vignettes thus open up a new, supplementary perspective, in which the traces that leadership practices have left on school participants are revealed.
Phenotype of adults with the 22q11 deletion syndrome: A review.

22q11 deletion syndrome (22qDS) is due to microdeletions of chromosome region 22q11.2. Little is known about the phenotype of adults. We reviewed available case reports of adults (age >/=18 years) with 22qDS and compared the prevalence of key findings to those reported in a large European survey of 22qDS (497 children and 61 adults) [Ryan et al., 1997: J. Med. Genet. 34:798-804]. Fifty-five studies reported on 126 adults (83 women, 40 men, 3 unknown sex), mean age 29.6 years (SD = 8.7 years). Compared with the European survey, adults with 22qDS reviewed had a lower rate of CHD, 30% versus 75%; chi(2) = 88.65, df = 1, P < 0.0001, but higher rates of identified palate anomalies, 88% versus 15%; chi(2) = 37.45, df = 1, P < 0.0001, and learning difficulties, 94% versus 79%; chi(2) = 12.13, df = 1, P = < 0.0008. The most common finding reported was minor facial anomalies. Few reports provided details of minor physical anomalies. Psychiatric conditions were more prevalent, 36% versus 18%; chi(2)= 5.71, df = 1, P < 0.02, than in the survey: 60% of reviewed adults were transmitting parents (72% mothers) ascertained following diagnosis of affected offspring. They had lower rates of CHD, cleft palate, and psychiatric disorders but similar rates of learning disabilities, and other palate and facial anomalies compared with adults ascertained by other methods. The results suggest that learning disabilities and facial and palate anomalies may be key findings in 22qDS adults, but that ascertainment is a key factor in the observed phenotype. Comprehensive studies of adults with 22qDS identified independently of familial transmission are necessary to further delineate the phenotype of adults and to determine the natural history of the syndrome.
The Occurrence of Potential Patient Safety Events Among Trauma Patients: Are They Random?

Objective:The Patient Safety Indicators (PSIs) from the Agency for Healthcare Research and Quality are validated measures of quality of care. The pattern of PSIs among adult trauma patients is unknown. Hypothesis:The occurrence of PSI events should be random and have no identifiable pattern across age, gender, and racial groups in trauma, because trauma services are designed to be an equal-access system. Design:Retrospective analysis of a nationally representative dataset. Setting:Nationwide Inpatient Sample (representative 20% sample from 37 states) for 5 years (2000 through 2004). Patients:Patients aged ≥18 admitted primarily for trauma. Outcomes:Occurrence of at least one of the applicable PSIs on multiple logistic regression analysis, with confirmation by sensitivity analysis. Results:A total of 1.35 million trauma patients were identified, with 19,338 patients (1.43%) experiencing at least one of the applicable PSIs. On multivariate analysis, controlling for injury severity and disease comorbidity, the adjusted odds ratios (ORs) for occurrence of at least 1 applicable PSI were noted to increase for patients who are 1) above age 35, 2) male gender (OR 1.25, 95% CI 1.19–1.31), and 3) black (OR 1.20 vs. whites, 95% CI 1.10-1.30) but not for any other racial groups. These results did not change significantly on sensitivity analysis. Conclusions:Patients who are above age 35, male gender, and black are associated with increased likelihood of experiencing a patient safety event in trauma care. When all else is equal, black patients are approximately 20% more likely than any other racial groups to experience a patient safety event, even after controlling for injury severity and disease comorbidity. These findings can help institutions prioritize chart review-based investigations to determine potential targets of systems improvement.
Mechanism of microtubule kinesin ATPase.

A six-step mechanism is derived for the activation of kinesin K379 ATPase by microtubules. The data are fitted by the kinetic scheme [Formula see text] where T, D, and P refer to nucleotide triphosphate, nucleotide diphosphate, and inorganic phosphate, respectively; MtK refers to the complex of a K379 unit with the microtubule binding site. The initial binding and release steps, 1 and 6, are treated as rapid equilibria: k2 = 200 s-1, k3 = 100 s-1, k5 = 35-40 s-1, maximum steady-state rate = 25 s-1 (50 mM NaCl, 20 degrees C). k2 was obtained from the maximum rate of fluorescence enhancement with mant-ATP as substrate, k3 was obtained from the hydrolysis transient phase for ATP or mant-ATP, and k5 was obtained from the rate of decrease in fluorescence of mant-ADP in the reaction [Formula see text]. A large excess of ATP was present with the Mt to block rebinding of mant-ADP. The rate was measured as a function of microtubule concentration and extrapolated to give the maximum rate k5. The same method was used to obtain k5 for ADP by mixing K.ADP with microtubules plus excess mant-ATP. The enhancement of fluorescence for the binding of mant-ATP is followed by a decrease in fluorescence with a rate constant of 35-40 s-1. Since the decrease must occur after hydrolysis, it may be correlated with a step or steps leading to the low fluorescence MtK.D state. In the kinetic scheme, steps 4 and 5 both contribute to determining the maximum turnover rate. At higher ionic strengths or lower protein concentrations, the MtK complex is dissociated by ATP. The maximum rate is 12 +/- 2 s-1 in 50 mM NaCl; consequently, hydrolysis occurs before dissociation. The dissociation constant of MtK in the presence of ADP is twice as large as the dissociation constant in the presence of ATP and four times larger than the KM for microtubule activation. The proposed kinetic scheme, which treats the K379 units of a dimer as independent, provides a satisfactory description of the transient and steady-state properties of the system with the possible exception of results at very low substrate concentrations.
Fetal Medicine Foundation fetal and neonatal population weight charts

To develop fetal and neonatal population weight charts. The rationale was that, while reference ranges of estimated fetal weight (EFW) are representative of the whole population, the traditional approach of deriving birth‐weight (BW) charts is misleading, because a large proportion of babies born preterm arise from pathological pregnancy. We propose that the reference population for BW charts, as in the case of EFW charts, should comprise all babies at a given gestational age, including those still in utero.
Age and gender variation in the impact of household structure on elderly mortality.

BACKGROUND There is little information about the impact of household structure and composition on elderly mortality in developing countries. This study examines the impact of relationship to head of household, and the presence of co-resident spouses and sons on elderly mortality in rural Bangladesh with a particular focus on age and gender differences. METHODS A total of 9365 individuals aged > or = 60 at baseline (5128 males and 4237 females) in the Matlab Surveillance area in rural Bangladesh were followed for a period of 8 years (1974-1982) with all predictors (the presence of a spouse, one or more co-resident adult sons, relationship to head of household, household economic status, age and disability status) being measured at the beginning of follow-up. Cox proportional hazard models were used in the analysis. RESULTS Being the head of household had a significant impact on reducing elderly mortality for both men and women. The presence of a spouse reduced mortality for all elderly men but had a significant beneficial impact only on women whose husbands were heads of households. Finally the presence of one or more co-resident adult sons reduced mortality for elderly women but not for elderly men. For all three of the above predictors there was a decline in effect with the age of the elderly. CONCLUSIONS Relationship to head of household and the presence of spouses and sons have powerful impacts on reducing mortality for elderly men and women in rural Bangladesh with the effects varying significantly by gender and age. Furthermore, individual rather than joint access to material resources is an important determinant of elderly mortality.
Essaying as method: Risky accounts and composing collectives

This essay moves between the performative, the discursive and the ethnographic to compose an argument about how essaying as method, and then collective essaying as method, might contribute to new approaches to world-making. It begins with an essay-within-an-essay that takes as its object of pressure the contemporary context of biophysical crisis that has been called the Anthropocene, which soon becomes entangled with another pair of objects: the image on the front of a vintage jigsaw set and the essayist's affective response to that image. Thereafter it brings in Latour's concept of the 'risky account' to argue for essaying as a reflexively constructed mode of making accounts of the world. The experimental nature of essaying is extrapolated into a collective context, with a report on a transcultural creative writing workshop conducted as part of a residency program in the Philippines. The essay proposes and teases out the concept of 'collective essaying'. It circles back to look at world making with Haraway's invocation of sympoesis as a method for 'worlding-with, in company' (Haraway 2015), and asks how collective essaying might be considered in this light.
Working While Studying: A Bad Decision?

I analyze the effect of working while studying on the performance of Spanish students in upper secondary education. Using education and labor histories, I construct the students’ grade performance as passing, repeating, or dropping out. I estimate the effect of working while studying from the first year the students are enrolled through their year of graduation. I find that working while studying substantially reduces the probability of passing and increases the probability of repeating or dropping out during their first year of upper secondary education. Not accounting for selection into working while studying would lead to underestimating the detrimental effect of working. Sensitivity analysis shows that the results are robust.
An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells

ABSTRACT Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing. Selected candidate lncRNAs were further characterized by PCR, gene-ontology analysis, and targeted bisulfite sequencing. Differential expression in response to therapy was observed more frequently in cis-acting than in overlapping lncRNAs (78% vs. 22%, fold change ≥1.5), while significantly altered methylation profiles were more commonly associated with overlapping lncRNAs (29% vs. 8%; P value <0.001). Moreover, overlapping lncRNAs contain more CpG islands (CGIs) (25% vs. 17%) and the majority of CGI-containing overlapping lncRNAs share these CGIs with their associated coding genes (84%). The differences in expression between sensitive and resistant cell lines were replicated in 87% of the selected candidates (P<0.05), while our bioinformatics approach identifying differential methylation was confirmed in all of the selected lncRNAs (100%). Five lncRNAs under epigenetic regulation appear to be involved in cisplatin resistance (AC091814.2, AC141928.1, RP11-65J3.1-002, BX641110, and AF198444). These novel findings provide new insights into epigenetic mechanisms and acquired resistance to cisplatin that highlight specific lncRNAs, some with unknown function, that may signal strategies in epigenetic therapies.
A Challenging State of Affairs: Public Administration in the Republic of Lebanon

ABSTRACT This article highlights Lebanon’s administrative challenges and reform efforts, since the end of its Civil War (1975–1990). In recent years, Lebanon and international donors have worked to improve transparency, promote modern management techniques, and encourage the use of information technology throughout the public sector. Despite these efforts, Lebanon’s public institutions remain constrained by the centralization of power, corruption, outdated bureaucratic structures, and deficiencies in administrative knowledge. The success of future reform efforts will depend on whether the Lebanese bureaucracy can overcome the challenges created by regional political tensions, its Syrian refugee crisis, and an increasingly indifferent Lebanese public.
Recognition of Resveratrol by the Human Estrogen Receptor-Alpha: A Molecular Modeling Approach to Understand Its Biological Actions

Objectives: Resveratrol (RSVL) is an edible phytoestrogen with multifaceted health benefits that may originate from binding to the estrogen receptors. Despite its structural similarity to the estrogen receptor-α (ERα) agonist diethylstilbestrol (DES), RSVL showed distinct biological profiles in estrogen-responsive biological systems. The molecular basis of such biological profiles has been undefined. Methods: We considered possible orientations for RSVL in ERα binding pocket. These conformations have been analyzed based on: (i) alignment with the key pharmacophoric elements of DES; (ii) computational energy of interaction, and (iii) pattern of accommodation at the ERα binding pocket. The characteristics of the most favored RSVL orientation have been compared with those of DES. Results: Both RSVL and DES interacted with the catalytic amino acid triad of the ERα pocket (His524, Arg394 and Glu 353). However, unlike the Erα agonists DES and estradiol (E2), RSVL formed three additional hydrogen bonds with Gly521 and Leu525, two paramount ligand recognition residues, and with Met343 at the ERα binding cavity. Lastly, RSVL displayed a more favorable energy of interaction with the ERα binding cavity. Conclusions: The present study suggests, for the first time, that RSVL is well recognized by the human ERα but in a manner distinct from the pure agonists DES and E2. These variations may well entail the unique biological responses of RSVL in ER-responsive systems.
Induction and contribution of beta platelet‐derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice

Hepatic stellate cells (HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of beta platelet‐derived growth factor (β‐PDGFR), which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal β‐PDGFR expression. While the role of β‐PDGFR is well established in liver injury, its expression and contribution during liver regeneration are unknown. The aim of this study was to determine whether β‐PDGFR is induced during liver regeneration following partial hepatectomy (pHx), and to define its contribution to the regenerative response.