Miracle-dz/UniFAR-FTUs huggingface dataset:
Increasing the power of the Mann‐Whitney test in randomized experiments through flexible covariate adjustment

The Mann‐Whitney U test is frequently used to evaluate treatment effects in randomized experiments with skewed outcome distributions or small sample sizes. It may lack power, however, because it ignores the auxiliary baseline covariate information that is routinely collected. Wald and score tests in so‐called probabilistic index models generalize the Mann‐Whitney U test to enable adjustment for covariates, but these may lack robustness by demanding correct model specification and do not lend themselves to small sample inference. Using semiparametric efficiency theory, we here propose an alternative extension of the Mann‐Whitney U test, which increases its power by exploiting covariate information in an objective way and which lends itself to permutation inference. Simulation studies and an application to an HIV clinical trial show that the proposed permutation test attains the nominal Type I error rate and can be drastically more powerful than the classical Mann‐Whitney U test. Copyright © 2014 John Wiley & Sons, Ltd.
Defining Patient Complexity From the Primary Care Physician's Perspective

BACKGROUND Patients with complex health needs are increasingly the focus of health system redesign. OBJECTIVE To characterize complex patients, as defined by their primary care physicians (PCPs), and to compare this definition with other commonly used algorithms. DESIGN Cohort study. SETTING 1 hospital-based practice, 4 community health centers, and 7 private practices in a primary care network in the United States. PARTICIPANTS 40 physicians who reviewed a random sample of 120 of their own patients. MEASUREMENTS After excluding patients for whom they were not directly responsible, PCPs indicated which of their patients they considered complex. These patients were characterized, independent predictors of complexity were identified, and PCP-defined complexity was compared with 3 comorbidity-based methods (Charlson score, Higashi score, and a proprietary Centers for Medicare & Medicaid Services algorithm). RESULTS Physicians identified 1126 of their 4302 eligible patients (26.2%) as complex and assigned a mean of 2.2 domains of complexity per patient (median, 2.0 [interquartile range, 1 to 3]). Mental health and substance use were identified as major issues in younger complex patients, whereas medical decision making and care coordination predominated in older patients (P<0.001 for trends by decade). Major independent predictors of PCP-defined complexity (P<0.001) included age (probability of complexity increased from 14.8% to 19.8% with age increasing from 55 to 65 years), poorly controlled diabetes (from 12.7% to 47.6% if hemoglobin A1c level≥9%), use of antipsychotics (from 12.7% to 31.8%), alcohol-related diagnoses (from 12.9% to 27.4%), and inadequate insurance (from 12.5% to 19.2%). Classification agreement for complex patients ranged from 26.2% to 56.0% when PCP assignment was compared with each of the other methods. LIMITATION Results may not be generalizable to other primary care settings. CONCLUSION Primary care physicians identified approximately one quarter of their patients as complex. Medical, social, and behavioral factors all contributed to PCP-defined complexity. Physician-defined complexity had only modest agreement with 3 comorbidity-based algorithms. PRIMARY FUNDING SOURCE Partners Community Healthcare, Inc.
Effectiveness and duration of daptomycin therapy in resolving clinical symptoms in the treatment of complicated skin and skin structure infections*

ABSTRACT Objective: Compare the rapidity of the resolution of clinical signs and symptoms of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive organisms between daptomycin and comparator agents. Patients and methods: A subset of South African patients with Gram-positive cSSSIs and no or one comorbid condition from two phase III clinical trials were included in the analysis. Patients were treated with daptomycin (n = 174) or comparator (penicillinase-resistant penicillins [n = 146] or vancomycin [n = 6]). The presence and severity of eight clinical signs and symptoms were evaluated at baseline, day 3 or 4 of treatment, end of therapy, and at test of cure (6–20 days after the last dose). Results: Of the 326 patients included in this analysis, the clinical success rates between daptomycin and comparator treatments was comparable. Overall, the severity of symptoms in the daptomycin-treated patients improved more quickly ( p = 0.04) than comparator treatment. At the day 3/4 evaluation, of the eight signs and symptoms, severity significantly decreased for induration ( p = 0.03) and erythema ( p = 0.05); a statistical trend was noted for necrotic tissue ( p = 0.10) and edema ( p = 0.10) in daptomycin-treated patients. Daptomycin treatment resulted in a shorter median duration of therapy than those receiving comparator treatment (7 vs. 8 days, p < 0.0001). Both treatments were well tolerated. Conclusion: Daptomycin produced a more rapid clinical improvement than comparators, as evidenced by significant reductions in the severity of induration and erythema, with a shorter duration of antibiotic therapy. However, this population was relatively young and healthy; therefore, these results may not be generalizable to all populations.
Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells

ABSTRACT Pneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bind in vitro to epithelial cells depends on the genetic background and the capsular serotype of the strain.
Spectroscopic observation of matrix-isolated carbonic acid trapped from the gas phase.

) is of fundamental importance, forexample,forregulationofbloodpH,intheacidificationoftheoceans, and in the dissolution of carbonates. This six-atommolecule commonly found in carbonated drinks in submicro-molar concentrations has so far eluded most attempts atisolation and direct detection. Despite the widespread beliefthat it is a highly instable molecule, the pure solid could beprepared previously,
Relationship Between Asymmetric Central Corneal Thickness and Glaucomatous Visual Field Loss Within the Same Patient

Purpose. Considering that thinner central corneal thickness (CCT) has been identified as a significant glaucoma risk factor, this study was designed to determine whether patients with glaucoma with asymmetric CCT demonstrate greater visual field loss in their thinner CCT eye compared with their thicker CCT eye. Methods. Patient logs were used to retrospectively identify patients with primary open-angle glaucoma (POAG) and patients with normal-tension glaucoma (NTG) with CCT asymmetry of 10 &mgr;m or greater. Severity of glaucoma was determined using Advanced Glaucoma Intervention Study (AGIS) visual field scoring criteria. After statistical analysis was used to compare all thinner CCT eyes vs. corresponding thicker CCT eyes, subjects with worse visual field loss in the thinner CCT eye were compared with subjects with worse visual field loss in the thicker CCT eye. Subanalysis was then completed using only subjects with CCT asymmetry of 15 &mgr;m or greater. Results. In the 52 subjects who met all criteria for study inclusion, mean AGIS score was significantly higher in the thinner CCT eyes compared with the thicker CCT eyes. Subjects with higher AGIS score in their thinner CCT eye outnumbered subjects with higher AGIS score in their thicker CCT eye, with the differences approaching statistical significance in the full sample (p = 0.06) and achieving significance when analysis was limited to subjects with CCT asymmetry of 15 &mgr;m or greater (p = 0.001). Multivariate logistic regression analysis identified thinner CCT as the primary risk factor associated with higher AGIS score in subjects with CCT asymmetry of 15 &mgr;m or greater. Conclusion. These results correspond to prior reports implicating CCT as an independent risk factor for glaucomatous visual field loss. When significant CCT asymmetry is present in patients with glaucoma, the thinner CCT eye is at greater risk for more advanced visual field loss. The underlying nature of this increased risk is unknown, but further study into structural vulnerabilities associated with thinner CCT seems justified.
Effects of acetorphan, an antidiarrhoeal enkephalinase inhibitor, on oro‐caecal and colonic transit times in healthy volunteers

Acetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro‐caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total orocaecal times were 303 ± 32 min vs. 287 ± 27 min and colonic transit times 25.8 ± 5.8 h vs. 31.3 ± 5.5 h after acetorphan and placebo, respectively (means ± S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulfphasalazine and radiopaque markers methods can be simultaneously applied in the same study.
Quantum size effects and enhancement of the oscillator strength of excitons in chains of silicon atoms.

We have studied the size-dependent optical properties of confined excitons in chainlike Si-backbone polymers with 5-110 Si atoms. The blueshift of the lowest exciton state was observed with decreasing number of Si atoms. In chains having 20 Si atoms or less, the oscillator strength per Si atom for the lowest exciton linearly increases with increasing number of Si atoms. The radiative-decay rate of excitons is in proportion to the square of the number of Si atoms. These results are experimental evidence of the quantum size effect of excitons in chains of Si atoms
Platelet Factor XIII and Calpain Negatively Regulate Integrin αIIbβ3 Adhesive Function and Thrombus Growth*

Excessive accumulation of platelets at sites of athero-sclerotic plaque rupture leads to the development of arterial thrombi, precipitating clinical events such as the acute coronary syndromes and ischemic stroke. The major platelet adhesion receptor glycoprotein (GP) IIb–IIIa (integrin αIIbβ3) plays a central role in this process by promoting platelet aggregation and thrombus formation. We demonstrate here a novel mechanism down-regulating integrin αIIbβ3 adhesive function, involving platelet factor XIII (FXIII) and calpain, which serves to limit platelet aggregate formation and thrombus growth. This mechanism principally occurs in collagen-adherent platelets and is induced by prolonged elevations in cytosolic calcium, leading to dramatic changes in platelet morphology (membrane contraction, fragmentation, and microvesiculation) and a specific reduction in integrin αIIbβ3 adhesive function. Adhesion receptor signal transduction plays a major role in the process by sustaining cytosolic calcium flux necessary for calpain and FXIII activation. Analysis of thrombus formation on a type I fibrillar collagen substrate revealed an important role for FXIII and calpain in limiting platelet recruitment into developing aggregates, thereby leading to reduced thrombus formation. These studies define a previously unidentified role for platelet FXIII and calpain in regulating integrin αIIbβ3 adhesive function. Moreover, they demonstrate the existence of an autoregulatory feedback mechanism that serves to limit excessive platelet accumulation on highly reactive thrombogenic surfaces.
Hypokalemia in Chinese peritoneal dialysis patients: prevalence and prognostic implication.

BACKGROUND Abnormal potassium metabolism may contribute to the increased cardiac morbidity and mortality seen in dialysis patients. We studied the pattern of serum potassium levels in a cohort of Chinese peritoneal dialysis (PD) patients. METHODS We studied serum potassium levels of 266 PD patients during 3 consecutive clinic visits. Dialysis adequacy, residual renal function, and nutritional status also were assessed. Patients were followed up for 33.7 +/- 20.7 months. RESULTS Mean serum potassium level was 3.9 +/- 0.5 mEq/L (mmol/L). Five patients (1.9%) had an average serum potassium level less than 3 mEq/L (mmol/L), whereas 54 patients (20.3%) had a serum potassium level less than 3.5 mEq/L (mmol/L). Serum potassium levels correlated with overall Subjective Global Assessment score (r = 0.276; P < 0.001) and serum albumin level (r = 0.173; P = 0.005) and inversely with Charlson comorbidity score (r = -0.155; P = 0.011). There was no correlation between serum potassium level and daily PD exchange volume, total Kt/V, urine volume, or residual glomerular filtration rate. By means of multivariate analysis with Cox proportional hazard model to adjust for confounders, serum potassium level was an independent predictor of actuarial patient survival. PD patients with hypokalemia (serum potassium < 3.5 mEq/L [mmol/L]) had significantly worse actuarial survival (hazard ratio, 1.79; 95% confidence interval, 1.12 to 2.85; P = 0.015) than those without hypokalemia after adjusting for confounding factors. CONCLUSION Hypokalemia is common in Chinese PD patients. Serum potassium level was associated with nutritional status and severity of coexisting comorbid condition. Furthermore, hypokalemia was an independent predictor of survival in PD patients. Additional studies may be needed to investigate the benefit of potassium supplementation for PD patients with hypokalemia.
Efficient computation of the one-step robust sets for piecewise affine systems with polytopic additive uncertainties

We propose a modification of the existing algorithm for computing the one-step robust sets for the discrete-time piecewise affine (DTPWA) systems subject to additive polytope-bounded uncertainties. In the old algorithm the Minkowski set difference between a union of polytopes (the so-called P-collection) and a polytope needs to be computed, which in turn calls twice for the computation of the set difference between a polytope and a P-collection. These set operations become computationally very demanding with the increasing number of polytopes in the P-collection and thus limit the practical applicability of the algorithm. In this paper we propose a more efficient procedure that avoids explicit evaluation of the Minkowski set difference. Our algorithm, on average, significantly reduces the complexity of the computation. We illustrate this on several examples of DTPWA systems for which the maximal robust positively invariant set is computed.
Results of Laparoscopic Versus Open Cholecystectomy in a Community Hospital

In a retrospective study, the first 301 patients who had laparoscopic cholecystectomy (LC) in a university-affiliated community hospital were compared with a historical matched control group of patients who had open cholecystectomy. The patients who had LC had a shorter hospital stay, required less postoperative pain medication, resumed normal activities and returned to work sooner, and had a lower minor and total complication rate. The mean operating time was 45 minutes longer for LC. Major complications, common bile duct injuries, and mortality were similar in both patient groups. The learning curve, use of laser, and use of cholangiography were all analyzed. Our results with LC compared favorably with results reported in the medical literature.
Effect of low‐level laser therapy on intramembranous and endochondral autogenous bone grafts healing

The aim of this study was to evaluate the healing process of intramembranous (IM) and endochondral (EC) bone grafts under low‐level laser therapy (LLLT). Male rabbits underwent onlay autogenous bone grafts (1 cm in diameter) retrieved from the calvaria and iliac crest and fixed on parietal bones, divided into four groups: Calvaria (C), Iliac (I), Calvaria + LLLT (C+L), and Iliac + LLLT (I+L). Animals from C+L and I+L Groups had their grafts exposed to LLLT (AlGaAs–808 nm, CW, 30 mW, 0.028 cm2 average laser beam area), 15 s irradiation time (16 J/cm2 per point–total of 64 J/cm2 per session). After 7, 14, 30, and 60 days, grafts were retrieved and resorption pattern analyzed by means of morphometry and TRAP‐positive osteoclasts detection. Differences in the resorption levels of iliac grafts were observed, presenting 40% in I group against 8% in I+L grafts at the 14th day of evaluation (P < 0.05). After 30 days, resorption was maintained at 41% in I group, whereas I+L presented 15% in the same period (P = 0.0591). No significant differences were noted in the rates of calvaria grafts resorption in all periods. A significant higher number of osteoclasts on the grafts' surface was observed in C+L Group at day 30, in comparison with C group. In I+L Group, prevalence of osteoclasts was marked at day 7 (P < 0.05) in comparison to I Group. In general, it was concluded that biomodulative effects of LLLT did not significantly affect healing and resorption processes of autogenous bone grafts from EC and IM origins. Microsc. Res. Tech. 75:1237–1244, 2012. © 2012 Wiley Periodicals, Inc.
Tracer vs. pressure wave velocities through unsaturated saprolite

Saprolite is a form of weathered bedrock that is commonly used as the host material at waste disposal sites in the Southeastern Piedmont. However, estimating the unsaturated hydraulic and transport properties of saprolite is difficult due to saprolite's low permeability. The authors demonstrate the use of short-duration fluid irrigation pulses for maintaining unsaturated conditions in intact saprolite columns. Concomitant Cl{sup {minus}} tracer experiments demonstrate that irrigated waters moved through an effective volumetric porosity substantially less than the ambient water-filled porosity. The authors observed the unexpected result that irrigation-induced pressure wave velocities were {approx}1,000 times faster than tracer velocities. The relationship between pressure wave velocities and fluid velocities is described using kinematic wave theory, presented for four parametric representations (Brooks-Corey, van Genuchten-Mualen, Broadbridge-White, and the Galileo Number), that predicts fluid pressure velocities to be from approximately two to fifteen times faster than saprolite tracer velocities. None of the kinematic models was able to reproduce observed rapid pressure wave velocities. A hydraulic form of the advection-diffusion equation based on Richards' equation is presented that favorably predicts the shape of pressure response curves only when the kinematic velocity is ignored and the hydraulic diffusivity of the unsaturated saprolite is considered. Based on themore » advection-diffusion equation, diffusion-dominated soil water pressure wave velocities should decrease with depth, eventually conforming with kinematic wave theory. Pressure pulse velocity monitoring may be an additional tool for estimating unsaturated hydraulic properties in low permeability media. « less
Characterization of diversity approaches for LFM stretch-processed waveforms

Frequency diversity in linear frequency modulated (LFM) waveforms can introduce unintended range shifts among receive radars in a distributed environment. This can make it difficult to predict where interference will occur in those receive radars, particularly when multipath is considered. This paper introduces the concept of interference region in range-frequency space to characterize the interference levels at a receive radar caused by waveforms transmitted from different radars in a distributed architecture. Linear frequency modulated (LFM) stretch-processed waveforms provide wide bandwidth and high range resolution while imposing only modest demands on the digital processing capabilities of a radar system. For this reason they are the waveform family of choice for many current wideband radar systems, including synthetic aperture radar (SAR) systems. However, LFM waveforms do not easily lend themselves to applications that require orthogonality, such as distributed radar architectures. The widespread use of these waveforms and the processing advantages they provide make it worthwhile to examine schemes for their use in a distributed environment. The paper uses interference region analysis to assess the effectiveness of frequency diversity, upchirp-downchirp diversity and chirp slope mismatch using LFM stretch-processed waveforms in a distributed environment.
Identification of Plant-derived Alkaloids with Therapeutic Potential for Myotonic Dystrophy Type I*

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3′ UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of available MBNL1 leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequestered MBNL1 from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1. We identified several alkaloids, including the β-carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of the DM1 pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases.